DOCSLIB.ORG

Neutrophils Chemotaxis and Phagocytosis in Human Coronin Function Is Required

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Neutrophils Chemotaxis and Phagocytosis in Human Coronin Function Is Required Coronin Function Is Required for Chemotaxis and Phagocytosis in Human Neutrophils This information is current as Ming Yan, Caterina Di Ciano-Oliveira, Sergio Grinstein and of September 23, 2021. William S. Trimble J Immunol 2007; 178:5769-5778; ; doi: 10.4049/jimmunol.178.9.5769 http://www.jimmunol.org/content/178/9/5769 Downloaded from References This article cites 25 articles, 11 of which you can access for free at: http://www.jimmunol.org/content/178/9/5769.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 23, 2021 *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 © 2007 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Coronin Function Is Required for Chemotaxis and Phagocytosis in Human Neutrophils1 Ming Yan,2 Caterina Di Ciano-Oliveira, Sergio Grinstein, and William S. Trimble3 Coronins are a family of conserved actin-associated proteins that have been implicated in a variety of cellular processes dependent on actin rearrangements. In this study, we show that in primary human neutrophils, coronins-1–4 and -7 are expressed. Coronin-1 accumulates at the leading edge of migrating neutrophils and at the nascent phagosome. Inhibition of coronin function by transduction of a dominant-negative form of the protein leads to inhibition of chemotaxis and a reduction in neutrophil spreading and adhesion. This inhibition appears to correlate with changes in the distribution of F-actin structures within the cell. In addition, phagocytosis is inhibited, but neither secretion nor activation of the NADPH oxidase appears to be affected. Together, these results show that coronins are required for actin-dependent changes in cell morphology that lead to migration and phagocytosis. The Journal of Immunology, 2007, 178: 5769–5778. Downloaded from hemotaxis is the directed migration of cells toward a gra- sion of coronin-1 includes a coiled coil domain implicated in tri- dient of a chemical attractant. In mammals, chemotaxis mer formation (6). ␤-propeller domains often represent interaction C plays an important role in a host of biological processes surfaces for protein-protein interactions, although it is not cur- ranging from development to innate immunity. In the case of the rently known what proteins bind to the coronin ␤-propeller do- immune system, many cells, but most notably neutrophils, effi- mains. Coronin-1 has been shown to associate with the Arp2/3 http://www.jimmunol.org/ ciently sense chemical gradients to migrate toward the sites of complex (7) and to F-actin (8, 9). In yeast, the Arp2/3 binding was injury or infection. This migratory response requires the develop- mapped to C-terminal coiled-coil region (10) and electron micros- ment of polarity within the neutrophil and unique actin structures copy indicated that this region bound near the p35 subunit of are assembled at the leading edge and rear of the cell to achieve Arp2/3 to cause a conformational change in the complex (11). The movement. Although many of the regulatory proteins contributing Arp2/3 binding region of mammalian coronin-1 has yet to be de- to the polarized accumulation of actin have been described, addi- termined. The regions of coronin-1 responsible for actin binding tional factors are likely to also contribute to this regulation. have been more controversial. Initial studies suggested that the One such actin-associated protein that may be important for strongest actin binding site was in the N-terminal 34 aa, while the neutrophil chemotaxis is coronin. Coronin was first described in second and third WD domains also had weak actin-binding capac- by guest on September 23, 2021 the slime mold Dictyostelium discoideum as a soluble protein that ity (9). More recently, studies have suggested that the C-terminal bound to actin-myosin complexes (1). Loss of the coronin gene half of the protein bound and cross-linked actin filaments (12) product results in cells with impaired chemotaxis and phagocytosis while deletion of residues 400–416 resulted in a protein that did (2). Coronins are conserved from yeast to humans, with at least not bind to the actin cytoskeleton (6). seven isoforms being expressed in mammals (3), but relatively The precise role of coronin in actin assembly also remains un- little is known about the specific roles of the mammalian forms or clear. In yeast, the coronin homolog Crn1p enhances barbed-end their functional relationship to the Dictyostelium form. assembly, apparently by reducing the lag phase of polymerization Recent structural studies of murine coronin-1 have revealed that (13). In contrast, Dictyostelium coronin associates with the entire the protein forms a seven-bladed ␤ propeller structure similar to length of actin filaments and it has been suggested to speed up the ␤ subunit of heterotrimeric G proteins (4). ␤ propellers are depolymerization (14). It has also been suggested that the phys- comprised of a protein domain called the WD domain, so-named ical association of coronin with the Arp2/3 complex alters the due to the presence of conserved tryptophan and aspartate residues, latter’s activity (10), by causing a conformational change in the and the WD domain folds such that it contributes to the formation complex (11). of two adjacent blades of the propeller (5). The C-terminal exten- Recently, we examined the role of coronin-1 in phagocytosis in the murine macrophage cell line RAW 264.7. Using a previously described dominant-negative fragment of coronin-1 (15) linked to Programme in Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada, the protein transducing domain of TAT, we were able to acutely and Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada inhibit the function of coronin (16). We showed that phagocytosis Received for publication May 5, 2006. Accepted for publication February 13, 2007. in this model system depended on functional coronin-1. Moreover, The costs of publication of this article were defrayed in part by the payment of page while binding to and signaling from the FcRs appeared normal, charges. This article must therefore be hereby marked advertisement in accordance and both actin and full-length (FL)4 coronin-1 accumulated at the with 18 U.S.C. Section 1734 solely to indicate this fact. phagocytic cup, the dominant-negative fragment prevented accu- 1 This work was supported by a grant from the Canadian Institutes of Health Re- search. S.G. is the current holder of the Pitblado Chair in Cell Biology. W.S.T. is a mulation of Arp2/3 and completion of phagocytosis. recipient of a Canada Research Chair in Molecular Cell Biology. 2 Current address: Division of Nephrology, Duke University Medical Center, Durham, NC 27708. 4 Abbreviations used in this paper: FL, full length; fMLF, N-formyl-Met-Leu-Phe; 3 Address correspondence and reprint requests to Dr. William S. Trimble, Programme RT, room temperature. in Cell Biology, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. E-mail address: [email protected] Copyright © 2007 by The American Association of Immunologists, Inc. 0022-1767/07/$2.00 www.jimmunol.org 5770 CORONIN IS REQUIRED FOR NEUTROPHIL CHEMOTAXIS In this study, we set out to examine the role of coronin in the (Qiagen). All RT-PCR products were detected on a 1% agarose gel and con- process of neutrophil chemotaxis. We first show that neutrophils firmed by DNA sequence analysis. PCR primers of all seven human coronin express five of the seven human coronin genes. We then demon- genes were follows as (using the nomenclature in Ref. 5; coronin-1 sense 5Ј-GCTGCACGAGCGGAGGTGTG-3Ј and antisense 5Ј-ATCCGAGCTG strate that coronin-1 transiently accumulates at the leading edge of GGAGTGCCAC-3Ј; coronin-2 sense 5Ј-TCCTTCCGCAAAGTGGTCCG-3Ј migrating neutrophils similar to F-actin. Moreover, by introducing and antisense 5Ј-AGGCTGTCCAGGCGGTACAG-3Ј; coronin-3 sense 5Ј-CA the dominant-negative fragment of coronin-1 into neutrophils, we GATTTGTTGCCATAATCATAGAG-3Ј and antisense 5Ј-TGATAATGGC observed significant changes in their adhesion properties and a ATTATCACAGCC-3Ј; coronin-4 sense 5Ј-ACAAAGGAGTCTGTCATCAC AAG-3Ј and antisense 5Ј-GCCATGGAATTGAAGATAGG-3Ј; coronin-5 nearly complete block in chemotaxis. Phagocytosis was also im- sense 5Ј-CCATCACCAAGAATGTGCAC-3Ј and antisense 5Ј-GCAGTCAA paired in these cells, but several other functions such as secretion TCATCTTCACCG-3Ј; coronin-6 sense 5Ј-ATCCGGCCAGGACGCCGAA and NADPH oxidase activation were unaffected. Our results dem- CC-3Ј and antisense 5Ј-ACCAGCTCGCACAGCATGTTC-3Ј; coronin-7 onstrate that coronin-1 plays a critical role in neutrophil adhesion sense 5Ј-GCCAGCTGCTCCTATATGAAG-3Ј and antisense 5Ј-TAGTC Ј and cell migration. CCACTCGTCCTCGTC-3 . Measurement of endogenous coronin concentration by Materials and Methods immunoblotting Reagents and Abs A total of 1.1 ϫ 106 neutrophils was lysed in 1 ml of boiling 1% SDS lysis All restriction enzymes were from New England Biolabs. DMEM, FBS, buffer, and passed five-time through a 27-gauge needle. A total of 2.5 ␮lof PBS, trypsin-EDTA, penicillin/streptomycin, and HEPES-buffered RPMI the neutrophil lysate (roughly 3000 cell equivalents) was subjected to SDS- 1640 were purchased from Wisent. Paraformaldehyde was obtained from PAGE on a 10% polyacrylamide gel.
Load more

Recommended publications
  • 1Β IL-12 Receptor Viral Inflammation Are Mediated Through Macrophage
    IL-12 p40 Homodimer-Dependent Macrophage Chemotaxis and Respiratory Viral Inflammation Are Mediated through IL-12 Receptor β1 This information is current as of September 24, 2021. Tonya D. Russell, Qingyun Yan, Guangshun Fan, Anthony P. Khalifah, D. Keith Bishop, Steven L. Brody and Michael J. Walter J Immunol 2003; 171:6866-6874; ; doi: 10.4049/jimmunol.171.12.6866 Downloaded from http://www.jimmunol.org/content/171/12/6866 References This article cites 63 articles, 41 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/171/12/6866.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 24, 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 © 2003 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology IL-12 p40 Homodimer-Dependent Macrophage Chemotaxis and Respiratory Viral Inflammation Are Mediated through IL-12 Receptor ␤11 Tonya D. Russell,* Qingyun Yan,* Guangshun Fan,* Anthony P.
    [Show full text]
  • Engineering 3D Systems with Tunable Mechanical Properties to Mimic the Tumor Microenvironment Shalini Raj Unnikandam Veettil Iowa State University
    Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2018 Engineering 3D systems with tunable mechanical properties to mimic the tumor microenvironment Shalini Raj Unnikandam Veettil Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Chemical Engineering Commons Recommended Citation Unnikandam Veettil, Shalini Raj, "Engineering 3D systems with tunable mechanical properties to mimic the tumor microenvironment" (2018). Graduate Theses and Dissertations. 17339. https://lib.dr.iastate.edu/etd/17339 This Thesis is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Engineering 3D systems with tunable mechanical properties to mimic the tumor microenvironment by Shalini Raj Unnikandam Veettil A thesis submitted to the graduate faculty in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Major: Chemical Engineering Program of Study Committee: Ian C Schneider, Major Professor Kaitlin Bratlie Michael Bartlett The student author, whose presentation of the scholarship herein was approved by the program of study committee, is solely responsible for the content of this thesis. The Graduate College will ensure this thesis is globally accessible and will not permit alterations after a degree is conferred. Iowa State University Ames, Iowa 2018 Copyright © Shalini Raj Unnikandam Veettil, 2018. All rights reserved. ii DEDICATION This thesis is dedicated to my family and friends who have been a great source of support.
    [Show full text]
  • The Role of 5-Lipoxygenase in Pathophysiology and Management of Neuropathic Pain
    REVIEW ARTICLE THE ROLE OF 5-LIPOXYGENASE IN PATHOPHYSIOLOGY AND MANAGEMENT OF NEUROPATHIC PAIN Pascanus Lamsihar PT∗, Faldi Yaputra∗∗, Jimmy FA Barus4 and I Putu Eka Widyadharma∗∗,1 ∗Department of Neurology, Provincial Mental Hospital, West Borneo, Indonesia., ∗∗Department of Neurology, Faculty of Medicine, Udayana University-Sanglah General Hospital, Bali, Indonesia., 4Department of Neurology, Faculty of Medicine, Atma Jaya Catholic University, Jakarta-Indonesia. ABSTRACT Neuropathic pain (NP) is a pain caused by lesions in the nervous system. Several causes of NP are traumatic, metabolic disorders, ischemia, toxins, infections, immune-related, and hereditary. The pathophysiology of NP is very complicated and unknown entirely. Therefore the treatment of NP is still unsatisfactory. Recent studies believed the critical role of primary inflammatory mediators in the pathophysiology of NP especially leukotrienes (LTs). The 5- lipoxygenase enzyme (5-LOX) is an enzyme that plays a role in the metabolism of arachidonic acid into LTs. Leukotrienes (LTs) are the essential inflammatory mediators in the pathophysiology of NP. Leukotriene B4 (LTB4) can cause chemotaxis on neutrophils, lowering nociceptors threshold and may contribute to NP. Several studies believed the administration of 5-LOX inhibitors or LTs receptor antagonists could be useful in the management of NP. The purpose of this review is to summarize the involvement of 5-LOX enzyme as an essential role in the pathophysiology and management of NP. KEYWORDS 5-lipoxygenase, leukotrienes,
    [Show full text]
  • Planarian Behavior: a Student-Designed Laboratory Exercise
    Planarian Behavior: A Student-Designed Laboratory Exercise Linda T. Collins and Brent W. Harker Department of Biological and Environmental Sciences University of Tennessee at Chattanooga Chattanooga, TN 37403 [email protected] Reprinted From: Collins, L. T. and B. W. Harker. 1999. Planarian behavior: A student-designed laboratory exercise. Pages 375-379, in Tested studies for laboratory teaching, Volume 20 (S. J. Karcher, Editor). Proceedings of the 20th Workshop/Conference of the Association for Biology Laboratory Education (ABLE), 399 pages. - Copyright policy: http://www.zoo.utoronto.ca/able/volumes/copyright.htm Although the laboratory exercises in ABLE proceedings volumes have been tested and due consideration has been given to safety, individuals performing these exercises must assume all responsibility for risk. The Association for Biology Laboratory Education (ABLE) disclaims any liability with regards to safety in connection with the use of the exercises in its proceedings volumes. © Linda T. Collins and Brent W. Harker Objectives 1. Know that different types of stimuli can affect planarian movement. 2. Distinguish between kinesis and taxis. 3. After preliminary observations, state a hypothesis to predict or explain planarian movement in response to an external stimulus. Test the hypothesis and reach a conclusion. Introduction Planarians are in the flatworm phylum, Platyhelminthes. Most planarians are free-living and are common in freshwater habitats. They are also found in marine and terrestrial environments. Planarians display bilateral symmetry, meaning the right and left halves are approximately mirror images of each other. The nervous system of planarians consists of an anterior “brain” consisting of large ganglia. Two ventral nerve cords run the length of the body from the ganglia.
    [Show full text]
  • PGE2 Signaling Via the Neuronal EP2 Receptor Increases Injury in a Model of Cerebral Ischemia
    PGE2 signaling via the neuronal EP2 receptor increases injury in a model of cerebral ischemia Qingkun Liua, Xibin Liangb, Qian Wanga, Edward N. Wilsona, Rachel Lamb, Jing Wanga, William Kongc, Connie Tsaia, Tingting Pana, Paul B. Larkina, Mehrdad Shamloob, and Katrin I. Andreassona,d,e,1 aDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA 94305; bDepartment of Neurosurgery, Comparative Medicine, and Neurology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305; cInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305; dStanford Neuroscience Institute, Stanford University, Stanford, CA 94305; and eStanford Immunology Program, Stanford University, Stanford, CA 94305 Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved April 9, 2019 (received for review November 4, 2018) The inflammatory prostaglandin E2 (PGE2) EP2 receptor is a master innate immunity (11), AD (4, 5, 12, 13), Parkinson’s disease (PD) suppressor of beneficial microglial function, and myeloid EP2 signal- (14, 15), and amyotrophic lateral sclerosis (16). More recently, ing ablation reduces pathology in models of inflammatory neurode- studies using myeloid cell conditional knockout strategies identified generation. Here, we investigated the role of PGE2 EP2 signaling in a EP2 receptor-driven pathologic microglial responses in models of model of stroke in which the initial cerebral ischemic event is fol- innate immunity, PD, and AD (4, 12, 15) where ablation of a lowed by an extended poststroke inflammatory response. Myeloid microglial EP2 receptor increased microglial chemotaxis and lineage cell-specific EP2 knockdown in Cd11bCre;EP2lox/lox mice at- phagocytosis and suppressed proinflammatory gene expression, tenuated brain infiltration of Cd11b+CD45hi macrophages and synaptic injury, and memory deficits.
    [Show full text]
  • Thiazolidine-2,4-Dione Attenuates Atherosclerosis Possibly by Reducing Monocyte Recruitment to the Lesion
    EXPERIMENTAL and MOLECULAR MEDICINE, Vol. 43, No. 8, 471-478, August 2011 5-(4-Hydroxy-2,3,5-trimethylbenzylidene) thiazolidine-2,4-dione attenuates atherosclerosis possibly by reducing monocyte recruitment to the lesion Jae-Hoon Choi1,2*, Jong-Gil Park2,3*, Accepted 20 June 2011 Hyung Jun Jeon2, Mi-Sun Kim4, Mi-Ran Lee2, Available Online 21 June 2011 2 2 5 Mi-Ni Lee , SeongKeun Sonn , Jae-Hong Kim , Abbreviations: 5-LOX, 5-lipoxygenase; BHB-TZD, 5-(3,5-di- Mun Han Lee3, Myung-Sook Choi6, tert-butyl-4-hydroxybenzylidene) thiazolidin-2,4-dione; COX, Yong Bok Park7, Oh-Seung Kwon8, cyclooxygenase; HMB-TZD, 5-(4-hydroxy-2,3,5-trimethyl- Tae-Sook Jeong9, Woo Song Lee10, Hyun Bo Shim2, benzylidene) thiazolidin-2,4-dione; ICAM-1, intercellular 4 2,11 adhesion molecule-1; Ldlr, low density lipoprotein receptor; Dong Hae Shin and Goo Taeg Oh TNF-α, tumor necrosis factor-alpha; VCAM-1, vascular cell adhesion molecule-1 1Department of Life Science College of Natural Sciences Hanyang University Abstract Seoul 133-791, Korea 2Division of Life and Pharmaceutical Sciences A variety of benzylidenethiazole analogs have been Ewha Womans University demonstrated to inhibit 5-lipoxygenase (5-LOX). Here Seoul 120-750, Korea we report the anti-atherogenic potential of 5-(4-hy- 3 Department of Veterinary Biochemistry droxy-2,3,5-trimethylbenzylidene) thiazolidin-2,4-di- College of Veterinary Medicine one (HMB-TZD), a benzylidenethiazole analog, and its Seoul National University potential mechanism of action in LDL receptor-defi- Seoul 151-742, Korea cient (Ldlr-/-) mice. HMB-TZD Treatment reduced leuko- 4Division of Life and Pharmaceutical Sciences triene B4 (LTB4) production significantly in RAW264.7 College of Pharmacy macrophages and SVEC4-10 endothelial cells.
    [Show full text]
  • Intrinsic 5-Lipoxygenase Activity Is Required for Neutrophil Responsivity
    Proc. Natl. Acad. Sci. USA Vol. 91, pp. 8156-8159, August 1994 Cell Biology Intrinsic 5-lipoxygenase activity is required for neutrophil responsivity DAVID M. GUIDOT, MICHAEL J. REPINE, JAY Y. WESTCOTT, AND JOHN E. REPINE Webb-Waring Institute for Biomedical Research and Department of Medicine, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Box C-321, Denver, CO 80262 Communicated by David W. Talmage, May 6, 1994 (receivedfor review March 9, 1994) ABSTRACT We found that intrinsic neutrophil 5-lipoxy- neutrophil-mediated injury in isolated lungs given IL-8 intra- genase activity was necessary for human neutrophil adherence tracheally. and chemotaxis in viro and human neutrophil-mediated acute edematous injury in isolated perfused rat lungs given interleu- kin 8 intratracheally. Treatment with either Zileuton (a specific MATERIALS AND METHODS reversible competitive inhibitor of 5-lipoxygenase) or MK886 Purification of Human Neutrophils. Heparinized blood was (a specific irreversible inhibitor ofthe 5-lipoxygenase activator obtained from healthy volunteers. Neutrophils were isolated protein) prevented stimulated neutrophil adherence and by using a Percoll gradient and differential centrifugation. chemotaxis (but not superoxide anion production) in vitro. Each preparation contained highly purified (>99%o) neutro- Zileuton- or MK886-inhibited neutrophil chemotaxis was not phils that were suspended in Hanks' balanced salt solution restored by adding leukotriene B4 in vitro. Perfusion with (Sigma) at a concentration of
    [Show full text]
  • Inflammation, Cancer and Oxidative Lipoxygenase Activity Are Intimately Linked
    Cancers 2014, 6, 1500-1521; doi:10.3390/cancers6031500 OPEN ACCESS cancers ISSN 2072-6694 www.mdpi.com/journal/cancers Review Inflammation, Cancer and Oxidative Lipoxygenase Activity are Intimately Linked Rosalina Wisastra and Frank J. Dekker * Pharmaceutical Gene Modulation, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands; E-Mail: [email protected] * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +31-5-3638030; Fax: +31-5-3637953. Received: 16 April 2014; in revised form: 27 June 2014 / Accepted: 2 July 2014 / Published: 17 July 2014 Abstract: Cancer and inflammation are intimately linked due to specific oxidative processes in the tumor microenvironment. Lipoxygenases are a versatile class of oxidative enzymes involved in arachidonic acid metabolism. An increasing number of arachidonic acid metabolites is being discovered and apart from their classically recognized pro-inflammatory effects, anti-inflammatory effects are also being described in recent years. Interestingly, these lipid mediators are involved in activation of pro-inflammatory signal transduction pathways such as the nuclear factor κB (NF-κB) pathway, which illustrates the intimate link between lipid signaling and transcription factor activation. The identification of the role of arachidonic acid metabolites in several inflammatory diseases led to a significant drug discovery effort around arachidonic acid metabolizing enzymes. However, to date success in this area has been limited. This might be attributed to the lack of selectivity of the developed inhibitors and to a lack of detailed understanding of the functional roles of arachidonic acid metabolites in inflammatory responses and cancer.
    [Show full text]
  • C5a Is Independent of Phospholipase Activation (Chemotactic Factors/Arachidonic Acid/Lipoxygenase/Chemotaxis/Human Neutrophils) ROBERT M
    Proc. Natl. Acad. Sci. USA Vol. 80, pp. 7200-7204, December 1983 Cell Biology Arachidonate metabolism by human polymorphonuclear leukocytes stimulated by N-formyl-Met-Leu-Phe or complement component C5a is independent of phospholipase activation (chemotactic factors/arachidonic acid/lipoxygenase/chemotaxis/human neutrophils) ROBERT M. CLANCY, CLEMENS A. DAHINDEN, AND TONY E. HUGLI Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, CA 92037 Communicated by HansJ. Muller-Eberhard, July 18, 1983 ABSTRACT Release of arachidonic acid by the membrane tactic factors appear capable of modulating a number of other phospholipase and metabolism by the 5-lipoxygenase pathway was aspects of the inflammatory reaction. examined in human polymorphonuclear leukocytes (PMNs). The Recently, another class of chemotactic factor was described. 5-lipoxygenase pathway is activated when PMNs are given arach- The biologically active principle, leukotriene B4 (LTB4), is a idonic acid in ethanol and there is extensive metabolism to 5-hy- complex lipid found to be as potent on a molar basis as the for- droxyicosatetraenoic acid (5-HETE) and leukotriene B4 (LTB4). myl peptides or C5a (7-9). LTB4 is a metabolite of arachidonic This activation event was shown to be altered by the ethanol be- acid formed by the 5-lipoxygenase pathway. Arachidonic acid cause resting PMNs given arachidonic acid with bovine serum al- does not exist in free form but is normally esterified in tri- bumin fail to metabolize arachidonic acid. However, cells acti- vated by the inflammatory agents N-formyl-Met-Leu-Phe (fMLF) glycerides and phospholipids in the cell membrane. It has been or complement component C5a recruit the 5-lipoxygenase to me- postulated that granulocyte stimulation activates membrane tabolize exogenous arachidonic acid to 5-HETE and LTB4.
    [Show full text]
  • Proresolving Mediators Resolution in the Mucosa
    Antimicrobial Aspects of Inflammatory Resolution in the Mucosa: A Role for Proresolving Mediators This information is current as Eric L. Campbell, Charles N. Serhan and Sean P. Colgan of September 28, 2021. J Immunol 2011; 187:3475-3481; ; doi: 10.4049/jimmunol.1100150 http://www.jimmunol.org/content/187/7/3475 Downloaded from References This article cites 85 articles, 36 of which you can access for free at: http://www.jimmunol.org/content/187/7/3475.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 28, 2021 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 © 2011 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Antimicrobial Aspects of Inflammatory Resolution in the Mucosa: A Role for Proresolving Mediators Eric L. Campbell,* Charles N. Serhan,† and Sean P. Colgan* Mucosal surfaces function as selectively permeable bar- what endogenous mechanisms control the magnitude and riers between the host and the outside world.
    [Show full text]
  • Biochemistry of the Eicosanoids: Cyclooxygenase and Lipoxygenase Products of Polyunsaturated Fatty Acids
    Lipids in Modern Nutrition, edited by M. Horisberger and U. Bracco. Nestle Nutrition, Vevey/Raven Press, New York © 1987. Biochemistry of the Eicosanoids: Cyclooxygenase and Lipoxygenase Products of Polyunsaturated Fatty Acids Elisabeth Granstrom Department of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden Certain polyunsaturated fatty acids can be metabolized by oxygenation into a large family of biologically active substances, the so-called prostanoids or eicosa- noids. This family includes the prostaglandins, thromboxanes, prostacyclins, leu- kotrienes, lipoxins, and also a number of related mono-, di-, and trihydroxy com- pounds as well as epoxygenated fatty acids. Most of these substances are potent compounds and display a wide variety of effects in many biological systems. Among these are effects on blood pressure, smooth muscle contractility, kidney function, cyclic nucleotide levels, glandular excretion, hormone secretion, platelet aggregation, vessel tone, temperature regu- lation, lipolysis, chemotaxis, immune response, cell growth and differentiation, electrolyte and water balance, etc. In combination with the fact that the eicosa- noids are almost ubiquitous in the mammalian body, it is not surprising that these substances are supposed to be involved in many physiological as well as pathologi- cal conditions in the organism. Thus, altered eicosanoid levels are sometimes found to coincide with the appearance of certain symptoms, and normalization oc- curs upon successful treatment of the condition with drugs
    [Show full text]
  • Specialized Pro-Resolving Mediators and the Lymphatic System
    International Journal of Molecular Sciences Review Specialized Pro-Resolving Mediators and the Lymphatic System Jamie D. Kraft 1,2, Robert Blomgran 3, Iben Lundgaard 4,5, Marianne Quiding-Järbrink 6, Jonathan S. Bromberg 7,8,9,10 and Emma Börgeson 1,2,11,* 1 Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden; [email protected] 2 Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 40530 Gothenburg, Sweden 3 Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Faculty of Medicine and Health Sciences, Linköping University, 58185 Linköping, Sweden; [email protected] 4 Department of Experimental Medical Science, Lund University, 22100 Lund, Sweden; [email protected] 5 Wallenberg Centre for Molecular Medicine, Lund University, 22100 Lund, Sweden 6 Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden; [email protected] 7 Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; [email protected] 8 Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA 9 Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USA 10 Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD 21201, USA 11 Region Vaestra Goetaland, Department of Clinical Physiology, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden Citation: Kraft, J.D.; Blomgran, R.; * Correspondence: [email protected]; Tel.: +46-31-342-3833 Lundgaard, I.; Quiding-Järbrink, M.; Bromberg, J.S.; Börgeson, E.
    [Show full text]