DOCSLIB.ORG

For Systemic Lupus Erythematosus Cells in the Target Organs in A

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
For Systemic Lupus Erythematosus Cells in the Target Organs in A Defective B1 Cell Homing to the Peritoneal Cavity and Preferential Recruitment of B1 Cells in the Target Organs in a Murine Model for Systemic Lupus Erythematosus This information is current as of September 26, 2021. Toshihiro Ito, Sho Ishikawa, Taku Sato, Kenji Akadegawa, Hideaki Yurino, Masahiro Kitabatake, Shigeto Hontsu, Taichi Ezaki, Hiroshi Kimura and Kouji Matsushima J Immunol 2004; 172:3628-3634; ; doi: 10.4049/jimmunol.172.6.3628 Downloaded from http://www.jimmunol.org/content/172/6/3628 References This article cites 26 articles, 8 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/172/6/3628.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 26, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2004 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Defective B1 Cell Homing to the Peritoneal Cavity and Preferential Recruitment of B1 Cells in the Target Organs in a Murine Model for Systemic Lupus Erythematosus1 Toshihiro Ito,*† Sho Ishikawa,* Taku Sato,* Kenji Akadegawa,* Hideaki Yurino,* Masahiro Kitabatake,* Shigeto Hontsu,*† Taichi Ezaki,‡ Hiroshi Kimura,† and Kouji Matsushima2* We previously reported that B lymphocyte chemoattractant (BLC; CXCL13) was highly and ectopically expressed in aged (NZB ؋ NZW)F1 (BWF1) mice developing lupus nephritis, and that B1 cells were preferentially chemoattracted toward BLC. We dem- onstrate in this study that B1 cells fail to home to the peritoneal cavity in aged BWF1 mice developing lupus nephritis, and that they are preferentially recruited to the target organs including the kidney, lung, and thymus when injected i.v. In contrast, B1 cells Downloaded from homed to the peritoneal cavity in aged BALB/c mice as effectively as in young mice. Accumulation of B1 cells to the omentum milky high high spots was also impaired in aged BWF1 mice compared with young mice. CD11b F4/80 cells with macrophage morphology were confirmed to be a major cell source for BLC in the peritoneal cavity both in young and aged BWF1 mice. However, the number of BLC-producing peritoneal macrophages was markedly decreased in aged BWF1 mice. These results suggest that the decreased number of BLC-producing peritoneal macrophages together with ectopic high expression of BLC in aged BWF1 mice result in abnormal B1 cell trafficking during the development of murine lupus. The Journal of Immunology, 2004, 172: 3628–3634. http://www.jimmunol.org/ ϫ he (NZB NZW)F1 (BWF1) strain of mice spontane- 7). Involvement of B1 cells in IgM-mediated autoimmune diseases ously develop systemic autoimmune disorders resembling such as autoimmune hemolytic anemia was also demonstrated (8, T systemic lupus erythematosus (SLE)3 in humans (1, 2). It 9). However, it remains to be elucidated whether B1 cells class- is characterized by production of a variety of IgG autoantibodies switch from IgM to IgG in the development of autoimmune dis- and massive deposition of immune complexes in glomeruli in the eases. Accumulating data also suggest that B1 cells contribute to kidney. More than 95% of these mice die from renal failure before the innate immunity by producing natural IgM Ab in the circula- 12 mo of age. A marked mononuclear cell infiltration in the target tion and by secreting IgA Ab in the intestinal mucosa (10–13). It by guest on September 26, 2021 organs, including the kidney and lung, is also observed in aged has been recently reported that BLC is essential for B1 cell homing BWF1 mice. We previously demonstrated that B lymphocyte che- to the peritoneal cavity and for body cavity immunity (14). In the moattractant (BLC; CXCL13) was highly and ectopically ex- present study, we investigated a role of BLC expression in aged pressed by myeloid dendritic cells in the target organs including BWF1 on aberrant B1 cell trafficking, including B1 cell homing to the thymus, kidney, and lung in aged BWF1 mice, but not in aged the peritoneal cavity. We found that B1 cell homing to the peri- NZB and NZW mice, and that B1 cells were preferentially che- toneal cavity was impaired and preferential B1 cell trafficking to moattracted toward BLC (3, 4). the target organs in aged BWF1 mice. We also demonstrated that B1 cells are a specialized cell population that are distinguished the number of BLC-producing peritoneal macrophages, which from conventional B cells (B2 cells) by their origin, cell surface were reported to be a major cell source for BLC in the peritoneal phenotype, unique tissue distribution, and capacity for self-re- cavity (14), was markedly decreased in aged BWF1 mice. Patho- newal, and have also been considered to be involved in autoanti- logical significance of abnormal B1 cell trafficking in the devel- body production in the development of autoimmune diseases (5– opment of murine lupus is discussed. *Department of Molecular Preventive Medicine, School of Medicine, University of Materials and Methods Tokyo, Tokyo, Japan; †Second Department of Internal Medicine, Nara Medical Uni- versity, Nara, Japan; and ‡Department of Anatomy and Developmental Biology, Mice School of Medicine, Tokyo Women’s Medical University, Tokyo, Japan ϫ (NZB NZW)F1 (BWF1), NZB, NZW, and BALB/c mice, originally Received for publication July 9, 2003. Accepted for publication January 20, 2004. obtained from the Shizuoka Laboratory Animal Center (Shizuoka, Japan), The costs of publication of this article were defrayed in part by the payment of page were maintained in our animal facility at University of Tokyo. Female charges. This article must therefore be hereby marked advertisement in accordance BWF1 and BALB/c mice aged 8–10 wk were used as young mice, and with 18 U.S.C. Section 1734 solely to indicate this fact. BWF1 mice aged 8–12 mo with moderate-to-severe proteinuria and 1 This work was supported by Solution-Oriented Research for Science and Technol- BALB/c mice aged 8 mo were used as aged mice. ogy (Japan Science and Technology Corporation) and the Long-Range Research Ini- tiative (Japan). Antibodies 2 Address correspondence and reprint requests to Dr. Kouji Matsushima, Department of Molecular Preventive Medicine, School of Medicine, University of Tokyo, 7-3-1 Hongo, Rat mAbs specific for mouse CD11b (M1/70), CD11c (HL-3), B220/ Bunkyo-ku, Tokyo 113-0033, Japan. E-mail address: [email protected] CD45R (RA3-6B2), CD5 (53-7.3RRH), MHC class II (ER-TR3), and 3 Abbreviations used in this paper: SLE, systemic lupus erythematosus; BLC, B lym- CD16/32 (2.4G2) were purchased from BD PharMingen (San Diego, CA). phocyte chemoattractant; pAb, polyclonal Ab; PBLk, peripheral blood leukocyte; Anti-F4/80 (CI: A3-1) mAb and goat anti-BLC polyclonal Ab (pAb) were CMTMR, 5-(and-6)-(((4-chloromethyl)benzoyl)amino)tetramethylrhodamine; purchased from Serotec (Raleigh, CA) and Genzyme Techne (Minneapolis, SDF-1, stromal cell-derived factor 1; SLC, secondary lymphoid tissue chemokine. MN), respectively. Copyright © 2004 by The American Association of Immunologists, Inc. 0022-1767/04/$02.00 The Journal of Immunology 3629 Downloaded from http://www.jimmunol.org/ FIGURE 1. Failure of B1 cell homing to the peritoneal cavity in aged BWF1 mice developing lupus nephritis. Four million CFSE-labeled peritoneal B1 ٗ Ⅵ ϫ 6 cells ( )or4 10 CMTMR-labeled splenic B2 cells ( ) suspended in 0.2 ml of PBS were injected i.v. into young BWF1 (A), aged BWF1 (B), young BALB/c (C), or aged BALB/c (D) mice. The recruitment to various lymphoid tissues was analyzed 24 h after injection. The results were presented as the Ϯ mean percentage SD in four independent experiments in BWF1 mice and in three in BALB/c mice. Note that B1 cells fail to home to the peritoneal cavity Ͻ ءءء Ͻ ءء Ͻ ء in aged BWF1 mice developing lupus nephritis. Statistical analysis was performed by Student’s t test. , p 0.03; , p 0.01; , p 0.001. PerC, Peritoneal cell; Thy, thymus; LN, lymph node; mLN, mesenteric lymph node; PP, Peyer patches; Spl, spleen. Cell preparation aged BWF1 mice labeled with CFSE and B1 cells from young BWF1 mice by guest on September 26, 2021 labeled with CMTMR suspended in 0.2 ml of PBS was injected i.v. into Peritoneal lavage cells were isolated by flushing the peritoneal cavity with young BWF1 mice. Mice were sacrificed 24 h after i.v. injection and sub- 4–6 ml of RPMI 1640 supplemented with 5% FCS. Cell suspensions pre- jected to flow-cytometric and immunofluorescent analysis. The number of pared from mouse spleen and lymph nodes were passed through nylon cells localized in the various organs was calculated by the percentage of mesh. Peripheral blood leukocytes (PBLk) were obtained by centrifugation labeled cells in each organ, and the percentage of recruited cells to the total on Lymphorite-M (Cedarlane, Hornby, Ontario, Canada). RBC in the number of injected cells was presented using an Epics Elite cell sorter. In spleen and PBLk were lysed by ammonium chloride solution. nonlymphoid organs, 10 nonconsecutive microscopic fields of cryostat sec- tion were examined, and the numbers of CFSE-labeled B1 cells and Flow cytometry CMTMR-labeled B2 cells in each field were counted.
Load more

Recommended publications
  • Milky Spots As the Implantation Site for Malignant Cells in Peritoneal Dissemination in Mice1
    ICANCKR RKSEARCH 53. 687-692. February I. 19931 Milky Spots as the Implantation Site for Malignant Cells in Peritoneal Dissemination in Mice1 Akeo Hagiwara,2 Toshio Takahashi, Kiyoshi Sawai, Hiroki Taniguchi, Masataka Shimotsuma, Shinji Okano, Chouhei Sakakura, Hiroyuki Tsujimoto, Kimihiko Osaki, Sadayuki Sasaki, and Morio Shirasu First Department of Surgery. Kyoto Prefectura! University ¡ifMedicine. Kawaramachi-Hirokoji, Kamigyo-ku Kyoto 602, Japan ABSTRACT MATERIALS AND METHODS We examined the site-specific implantation or cancer cells in peritoneal Animals and Cancer Cell Line. Five-week-old male CDF, mice (Shimi/u tissues after an i.p. inoculation of IO5 P388 leukemia cells. Twenty-four h Laboratory Animal Center, Kyoto, Japan) were maintained under standard after the inoculation, the numher of viable cancer cells infiltrating into conditions (specific pathogen free: 22°C;60% relative humidity; 12-h day- specific tissue sites of the peritoneum was estimated by an i.p. transfer night cycle). method. A descending order of tissue implantation with cancer cells was P388 leukemia cells were maintained through i.p. inoculation in DBA2Cr established as omentum > gonadal fat > mesenterium > posterior ab mice (Shimi/.u Laboratory Animal Center). The ascites containing P388 leu dominal wall > stomach, liver, intestine, anterior abdominal wall, and kemia cells was taken from the carrier mouse and suspended in saline at a lung. A significant correlation was established between the logarithm of concentration of IO7 P388 leukemia cells/ml. The viability of the tumor cells, the number of infiltrating cancer cells and the logarithm of the number of as determined by the trypan blue exclusion lest, was greater than 95%.
    [Show full text]
  • Analysis of Human Omentum-Associated Lymphoid Tissue Components with S-100: an Immunohistochemical Study
    Romanian Journal of Morphology and Embryology 2010, 51(4):759–764 ORIGINAL PAPER Analysis of human omentum-associated lymphoid tissue components with S-100: an immunohistochemical study A. YILDIRIM1), A. AKTAŞ2), Y. NERGIZ2), M. AKKUŞ2) 1)Department of Histology and Embryology, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey 2)Department of Histology and Embryology, Faculty of Medicine, Dicle University, Diyarbakir, Turkey Abstract Milky spots are opaque patches in the greater omentum. They were first described by von Recklinghausen (1863) in the omentum of rabbits. In man, milky spots are relatively uniform, highly vascularized accumulations of mononuclear cells. The objective of this study was to describe in human omental lymphoid tissue components with S-100. Tissue samples (greater omentum) were collected from 14 patients operated with different reasons in our Department of General Surgery, in order to histologically present the presence of S-100 in the cells making up the milky spots in human omentum tissue. Tissue samples were cut approximately 5–8 micrometer thick with frozen-sections and stained with an indirect immunoperoxidase technique, as described previously. Then milky spots were examined by light microscopy. These data indicate that unstimulated milky spots in the human greater omentum are to a great extent just a preformed specific accumulation of primarily macrophages within the stroma of the greater omentum, secondarily B- and T-lymphocytes. In addition to these cells, we observed that a few mast and reticular cells were seen in the milky spots by S-100 reactive cross-sections of greater omentum. In the human omentum tissue that was stained with indirect immunoperoxidase method using anti S-100 monoclonal antibody, an arteriole cross-section in the center, reactive nerve cross-sections in the adjacent stroma and endogenic peroxidase reactivity in a few granulocytes in omental tissue were observed.
    [Show full text]
  • Bone Marrow Adipocytes: a Link Between Obesity and Bone Cancer
    cancers Review Bone Marrow Adipocytes: A Link between Obesity and Bone Cancer Michaela R. Reagan 1,2,3,*, Heather Fairfield 1,2,3 and Clifford J. Rosen 1,2,3 1 Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine, ME 04074, USA; [email protected] (H.F.); [email protected] (C.J.R.) 2 School of Medicine, Tufts University, Boston, MA 02111, USA 3 Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME 04469, USA * Correspondence: [email protected]; Tel.: +1-207-396-8196 Simple Summary: This review discusses the important newly-established roles for bone marrow adipose tissue in cancer progression and highlights the research demonstrating great promise for clinically targeting the cells in oncology. Bone marrow adipose tissue expands during aging and in obesity. It primarily comprises bone marrow adipocytes (also known as fat cells) and can also contain other cells, such as pre-adipocytes, fibroblasts, macrophages, other immune cells, and endothelial cells. Bone marrow adipocytes are scattered throughout the hematopoietic or “red” marrow, or are densely packed in the marrow cavity, creating “yellow” marrow. Bone marrow biologists are interrogating many questions to understand the nature of bone marrow adipocytes, including how aging and obesity affect these cells; their origins, functions, and endocrine roles; and whether they can be targeted to treat osteoporosis. In parallel, and often in concert, cancer researchers are delineating the role of bone marrow adipocytes in oncology and their potential translational significance for future therapeutics. Abstract: Cancers that grow in the bone marrow are for most patients scary, painful, and incurable.
    [Show full text]
  • Redalyc.Protective Compromise of Great Omentum in an Asymptomatic
    Revista Colombiana de Ciencias Pecuarias ISSN: 0120-0690 [email protected] Universidad de Antioquia Colombia González-Domínguez, María S; Hernández, Carlos A; Maldonado-Estrada, Juan G Protective compromise of great omentum in an asymptomatic uterine rupture in a bitch: a case report Revista Colombiana de Ciencias Pecuarias, vol. 23, núm. 3, julio-septiembre, 2010, pp. 369-376 Universidad de Antioquia Medellín, Colombia Available in: http://www.redalyc.org/articulo.oa?id=295023477012 How to cite Complete issue Scientific Information System More information about this article Network of Scientific Journals from Latin America, the Caribbean, Spain and Portugal Journal's homepage in redalyc.org Non-profit academic project, developed under the open access initiative González-Domínguez MS, et al. Asymptomatic uterine rupture in a bitch 369 Casos clínicos Revista Colombiana de Ciencias Pecuarias http://rccp.udea.edu.co CCP Protective compromise of great omentum in an asymptomatic uterine rupture in a bitch: a case report¤ Compromiso protector del omento mayor en una ruptura uterina asintomática en una perra: reporte de un caso Empenho protetor do omento maior em uma rotura uterina asymptomatica numa cadela: um porte de caso 1* 1 2 María S González-Domínguez , MV, Esp.; Carlos A Hernández , MV, MS; Juan G Maldonado-Estrada , MVZ, MS, PhD. 1Grupo de Investigación INCA-CES Facultad de Medicina Veterinaria y Zootecnia, Universidad CES; Medellín, Colombia. 2Grupo de Investigación CENTAURO, Escuela de Medicina Veterinaria, Universidad de Antioquia. Medellín, Colombia. (Recibido: 19 agosto, 2009; aceptado: 15 julio, 2010 ) Summary The great omentum plays an important role in protecting the peritoneal cavity from bacteria and contaminating material and providing the peritoneum with leukocytes from the omental milky spots (OMS).
    [Show full text]
  • Fat-Associated Lymphoid Clusters in Inflammation and Immunity
    MINI REVIEW published: 21 December 2016 doi: 10.3389/fimmu.2016.00612 Fat-Associated Lymphoid Clusters in inflammation and immunity Sara Cruz-Migoni* and Jorge Caamaño* College of Medical and Dental Sciences, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK Fat-associated lymphoid clusters (FALCs) are atypical lymphoid tissues that were originally identified in mouse and human mesenteries due to that they contain a high number of type 2 innate lymphoid cells/nuocytes/natural helper cells. FALCs are located on adipose tissues in mucosal surfaces such as the mediastinum, pericardium, and gonadal fat. Importantly, these clusters contain B1, B2 and T lymphocytes as well as myeloid and other innate immune cell populations. The developmental cues of FALC Edited by: formation have started to emerge, showing that these clusters depend on a different set Andreas Habenicht, of molecules and cells than secondary lymphoid tissues for their formation. Here, we Ludwig Maximilian University of Munich, Germany review the current knowledge on FALC formation, and we compare FALCs and omental Reviewed by: milky spots and their responses to inflammation. Mark Christopher Coles, Keywords: lymphoid tissues, fat-associated lymphoid clusters, peritoneal inflammation, peritoneal immune University of York, UK responses, tertiary lymphoid structures Andrea Brendolan, San Raffaele Hospital (IRCCS), Italy *Correspondence: Sara Cruz-Migoni INTRODUCTION [email protected]; Jorge Caamaño The interactions between different types of immune cells are essential for both innate and adaptive [email protected] immune responses to pathogens. Such interactions require strategically situated microenvironments to increase the chances that rare antigen-specific lymphocytes become activated.
    [Show full text]
  • Fat-Associated Lymphoid Clusters in Inflammation and Immunity Cruz-Migoni, Sara; Caamaño, Jorge
    University of Birmingham Fat-Associated Lymphoid Clusters in Inflammation and Immunity Cruz-migoni, Sara; Caamaño, Jorge DOI: 10.3389/fimmu.2016.00612 License: Creative Commons: Attribution (CC BY) Document Version Publisher's PDF, also known as Version of record Citation for published version (Harvard): Cruz-migoni, S & Caamaño, J 2016, 'Fat-Associated Lymphoid Clusters in Inflammation and Immunity', Frontiers in immunology, vol. 7, 612. https://doi.org/10.3389/fimmu.2016.00612 Link to publication on Research at Birmingham portal General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. •Users may freely distribute the URL that is used to identify this publication. •Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. •User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?) •Users may not further distribute the material nor use it for the purposes of commercial gain. Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document. When citing, please reference the published version. Take down policy While the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has been uploaded in error or has been deemed to be commercially or otherwise sensitive.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,513,208 B2 Nicolette Et Al
    USOO851.3208B2 (12) United States Patent (10) Patent No.: US 8,513,208 B2 Nicolette et al. (45) Date of Patent: Aug. 20, 2013 (54) TRANSIENT EXPRESSION OF Bessis et al., “Syngeneic fibroblasts transfected with a plasmid IMMUNOMODULATORY POLYPEPTIDES encoding interleukin-4 as non-viral vectors for anti-inflammatory FOR THE PREVENTION AND TREATMENT gene therapy in collagen-induced arthritis' J. Gene Med vol. 4, pp. 300-307 (2002). OF AUTOIMMUNE DISEASE, ALLERGY AND King et al., “TGF-beta1 alters APC preference, polarizing islet anti TRANSPLANT RELECTION genresponses toward a Th2 phenotype” Immunity vol. 8, pp. 601-613 (75) Inventors: Charles A. Nicolette, Durham, NC (US); (1998). C. Garrison Fathman, Portola Valley, Perone et al., “Dendritic cells expressing transgenic galectin-1 delay CA (US); Remi Creusot, San Francisco, onset of autoimmune diabetes in mice” J. Immunol. vol. 177, pp. CA (US) 5278-5289 (2006). (73) Assignees: Argos Therapeutics, Inc., Durham, NC Smith et al., “Localized expression of an anti-TNF single-chain anti (US); The Board of Trustees of the body prevents development of collagen-induced arthritis' Gene Ther: Leland Stanford Junior University, vol. 10, pp. 1248-1257 (2003). Palo Alto, CA (US) Creusotet al., “A shortpulse of Il-4 delivered by DCs electroporated (*) Notice: Subject to any disclaimer, the term of this with modified mRNA can both prevent and treat autoimmune diabe patent is extended or adjusted under 35 tes in NOD mice” Mol. Ther: vol. 18, No. 12, pp. 2112-2120 (Dec. 2010). U.S.C. 154(b) by 66 days. Falcone et al., “IL-4 triggers autoimmune diabetes by increasing (21) Appl.
    [Show full text]
  • Abnormal Development and Differentiation of Macrophages and Dendritic Cells in Viable Motheaten Mutant Mice Deficient in Haematopoietic Cell Phosphatase
    Int. J. Exp. Path. (1997), 78, 245–257 Abnormal development and differentiation of macrophages and dendritic cells in viable motheaten mutant mice deficient in haematopoietic cell phosphatase KEI-ICHIRO NAKAYAMA*†, KIYOSHI TAKAHASHI*, LEONARD D. SHULTZ§, KAZUHISA MIYAKAWA* AND KIMIO TOMITA† *Second Department of Pathology and †Third Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan and §The Jackson Laboratory, Bar Harbor, Maine Received for publication 29 January 1997 Accepted for publication 15 May 1997 Summary. In mice homozygous for the ‘viable motheaten’ (mev) mutation, numbers of macrophage progenitor cells, particularly monocytes, were markedly increased in the bone marrow and spleen. Increased mobilization of these precursor cells to peripheral tissues and their differentiation to macrophages were evidenced by striking increases in macrophage numbers. Immunohistochemical double staining of tissue sections and flow cytometry analyses of single cell suspensions from these mice demonstrated CD5 (Ly- 1)-positive macrophages in the peritoneal cavity, spleen and other tissues. Ly-1-positive macrophage precursor cells were demonstrated in the peri- toneal cavity of the mev mice and developed in the omental milky spots. The development of marginal metallophilic and marginal zone macrophages was poor in the splenic white pulp and related macrophage populations were absent in the other lymphoid tissues. The numbers of epidermal Langerhans cells in the skin and T cell-associated dendritic cells in the thymic
    [Show full text]
  • E2410-The Greater Omentum As a Site for Pancreatic Islet Transplantation
    CellR4 2017; 5 (3): e2410 The greater omentum as a site for pancreatic islet transplantation M. Pellicciaro1, I. Vella1, G. Lanzoni2, G. Tisone1, C. Ricordi2 1Liver Transplant Center, Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy. 2Diabetes Research Institute and Cell Transplant Center, University of Miami, Miami, FL, USA. Corresponding Author: Marco Pellicciaro, MD student; e-mail: [email protected] Keywords: Omentum, Greater omentum, Islet of Lang- fat tissue, and lymphoid aggregates called “milky erhans, Islet of Langerhans transplantation, T1D, Islet trans- spots”. Two monolayers of mesothelium contain plantation, Pancreatic islet transplantation, Diabetes type 1, all the above cell types and structures, with the Beta cell transplantation. exception of milky spots – where the mesotheli- um is interrupted. The macroscopic presentation ABSTRACT of the greater omentum depends on the age of The greater omentum is a highly vascularized the individual, nutrition, pathological conditions anatomical structure in the peritoneal cavity. Its and state of stimulation (such as in foreign body main components are connective, adipose and reactions, peritoneal dialysis). The right and left vascular cells, along with specialized immune Gastroepiploic arteries provide blood supply to cells. The omentum functions as a site for fat ac- the greater omentum. Both arteries derive from cumulation, it has adhesive properties to control the celiac trunk and pass the greater gastric cur- traumatized and inflamed tissues, and a function vature. They progressively branch out towards in local hemostasis, immune responses, and re- the stomach and the omentum, giving terminal vascularization. Other functions include the ab- vessels for the omentum through the right and left sorption of fluids, the phagocytosis of particulate epiploic arteries.
    [Show full text]
  • Characterization of Omental Immune Aggregates During Establishment of a Latent Gammaherpesvirus Infection
    Characterization of Omental Immune Aggregates during Establishment of a Latent Gammaherpesvirus Infection Kathleen S. Gray, Christopher M. Collins, Samuel H. Speck* Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America Abstract Herpesviruses are characterized by their ability to establish lifelong latent infection. The gammaherpesvirus subfamily is distinguished by lymphotropism, establishing and maintaining latent infection predominantly in B lymphocytes. Consequently, gammaherpesvirus pathogenesis is closely linked to normal B cell physiology. Murine gammaherpesvirus 68 (MHV68) pathogenesis in laboratory mice has been extensively studied as a model system to gain insights into the nature of gammaherpesvirus infection in B cells and their associated lymphoid compartments. In addition to B cells, MHV68 infection of macrophages contributes significantly to the frequency of viral genome-positive cells in the peritoneal cavity throughout latency. The omentum, a sheet of richly-vascularized adipose tissue, resides in the peritoneal cavity and contains clusters of immune cell aggregates termed milky spots. Although the value of the omentum in surgical wound-healing has long been appreciated, the unique properties of this tissue and its contribution to both innate and adaptive immunity have only recently been recognized. To determine whether the omentum plays a role in gammaherpesvirus pathogenesis we examined this site during early MHV68 infection and long-term latency. Following intraperitoneal infection, immune aggregates within the omentum expanded in size and number and contained virus-infected cells. Notably, a germinal- center B cell population appeared in the omentum of infected animals with earlier kinetics and greater magnitude than that observed in the spleen.
    [Show full text]
  • The Milky Spots of the Peritoneum and Pleura: Structure, Development and Pathology
    Biomedical Reviews 2004; 15: 47-66. Founded and printed in Varna, Bulgar ia ISSN 1310-392X THE MILKY SPOTS OF THE PERITONEUM AND PLEURA: STRUCTURE, DEVELOPMENT AND PATHOLOGY Krassimira N. Michailova and Kamen G. Usunoff Department of Anatomy and Histology, Faculty of Medicine, Medical University, Sofia, Bulgaria The milky spots (MS), originally described by Ranvier as taches laiteuses, are found on the greater omentum but also in other peritoneal regions, as well as on the pleura and pericardium. They represent aggregations of mesenchymal tissue surrounding blood vessels. These small whitish regions are covered by mesothelium, and within the mesothelial layer are scattered macrophage-like cells. The blood supply of MS is provided by arterioles that give rise to capillary network formed by fenestrated or continuous endothelial cells. Most MS possess also lymphatic vessels, with extremely thin endothelial cells. The most frequent cells in MS are the macrophages, followed by lymphocytes and mast cells. Typically, the macrophages are located in the periphery, while the lymphocytes - in the center of MS. Additional structural elements are plasmocytes, adipocytes, fibroblasts, rounded fibroblast-like cells (undifferentiated mesenchymal cells), as well as collagen, reticular and elastic fibers. The nerve fibers innervating MS are located under the mesothelium and among the free cells. Despite their small size, the MS are a significant organ, functioning at both normal and pathological conditions. Under inflammatory conditions (peritonitis), MS act as the first line of defense, and dramatically change their number, size and structure. MS are also involved in extramedullary hemopoiesis. They are the first target of intraperitoneal (intrapleural) metastases, and appear an important target in the development of immunotherapeutic strategies against malignant diseases.
    [Show full text]
  • Understanding Immune Cells in Tertiary Lymphoid Organ Development: It Is All Starting to Come Together
    REVIEW published: 03 October 2016 doi: 10.3389/fimmu.2016.00401 Understanding Immune Cells in Tertiary Lymphoid Organ Development: It Is All Starting to Come Together Gareth W. Jones*, David G. Hill and Simon A. Jones Division of Infection and Immunity, Systems Immunity URI, The School of Medicine, Cardiff University, Cardiff, UK Tertiary lymphoid organs (TLOs) are frequently observed in tissues affected by non-resolving inflammation as a result of infection, autoimmunity, cancer, and allograft rejection. These highly ordered structures resemble the cellular composition of lymphoid follicles typically associated with the spleen and lymph node compartments. Although TLOs within tissues show varying degrees of organization, they frequently display evi- dence of segregated T and B cell zones, follicular dendritic cell networks, a supporting stromal reticulum, and high endothelial venules. In this respect, they mimic the activities of germinal centers and contribute to the local control of adaptive immune responses. Studies in various disease settings have described how these structures contribute to Edited by: Andreas Habenicht, either beneficial or deleterious outcomes. While the development and architectural orga- Ludwig Maximilian University of nization of TLOs within inflamed tissues requires homeostatic chemokines, lymphoid Munich, Germany and inflammatory cytokines, and adhesion molecules, our understanding of the cells Reviewed by: responsible for triggering these events is still evolving. Over the past 10–15 years, novel Ingrid E. Dumitriu, St. George’s University of London, immune cell subsets have been discovered that have more recently been implicated in UK the control of TLO development and function. In this review, we will discuss the contribu- Nancy H.
    [Show full text]