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Mucosal Surfaces in Human Tissues Localization of Lung Surfactant Localization of Lung Surfactant Protein D on Mucosal Surfaces in Human Tissues Jens Madsen, Anette Kliem, Ida Tornøe, Karsten Skjødt, Claus Koch and Uffe Holmskov This information is current as of September 29, 2021. J Immunol 2000; 164:5866-5870; ; doi: 10.4049/jimmunol.164.11.5866 http://www.jimmunol.org/content/164/11/5866 Downloaded from References This article cites 42 articles, 17 of which you can access for free at: http://www.jimmunol.org/content/164/11/5866.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 29, 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 © 2000 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Localization of Lung Surfactant Protein D on Mucosal Surfaces in Human Tissues1 Jens Madsen,* Anette Kliem,* Ida Tornøe,* Karsten Skjødt,* Claus Koch,† and Uffe Holmskov2* Lung surfactant protein-D (SP-D), a collectin mainly produced by alveolar type II cells, initiates the effector mechanisms of innate immunity on binding to microbial carbohydrates. A panel of mRNAs from human tissues was screened for SP-D mRNA by RT-PCR. The lung was the main site of synthesis, but transcripts were readily amplified from trachea, brain, testis, salivary gland, heart, prostate gland, kidney, and pancreas. Minor sites of synthesis were uterus, small intestine, placenta, mammary gland, and stomach. The sequence of SP-D derived from parotid gland mRNA was identical with that of pulmonary SP-D. mAbs were raised against SP-D, and one was used to locate SP-D in cells and tissues by immunohistochemistry. SP-D immunoreactivity was found in alveolar type II cells, Clara cells, on and within alveolar macrophages, in epithelial cells of large and small ducts of the parotid Downloaded from gland, sweat glands, and lachrymal glands, in epithelial cells of the gall bladder and intrahepatic bile ducts, and in exocrine pancreatic ducts. SP-D was also present in epithelial cells of the skin, esophagus, small intestine, and urinary tract, as well as in the collecting ducts of the kidney. SP-D is generally present on mucosal surfaces and not restricted to a subset of cells in the lung. The localization and functions of SP-D indicate that this collectin is the counterpart in the innate immune system of IgA in the adaptive immune system. The Journal of Immunology, 2000, 164: 5866–5870. http://www.jimmunol.org/ ung surfactant protein D (SP-D)3 is one of the collectins, lysosomal granules of alveolar macrophages (18, 19), suggesting a a family of oligomeric proteins whose individual chains receptor-mediated uptake by these cells; a putative receptor for L consist of a collagen region linked to a C-type lectin do- SP-D, gp-340, has been characterized (20). SP-D also seems to main via an ␣ helical neck region (1, 2). The structural subunits of have an immunomodulatory function, inhibiting T lymphocyte SP-D are homotrimers of these chains, and the subunits are them- proliferation and IL-2 production (21) as well as inhibiting specific selves oligomerized into cross-like tetramers and higher oligomers IgE binding to allergens and blocking allergen-induced histamine (3–8). release from human basophils (13, 22). SP-D binds to oligosaccharides on the surface of a variety of In addition to its role in antimicrobial defense, SP-D may be pathogenic microorganisms. This binding initiates several effector involved in pulmonary surfactant homeostasis. It interacts with by guest on September 29, 2021 mechanisms, including the recruitment of inflammatory cells to phospho- and glycolipids in vitro (23–25), and mice made SP-D destroy the pathogens. SP-D has been shown to bind to carbohy- deficient by gene targeting accumulate surfactant lipids and alve- drate residues on influenza A virus, thereby inhibiting its hemag- olar macrophages in the alveolar space (26, 27). In this situation, glutination activity and causing viral aggregation (9, 10). SP-D the macrophages may appear as multinucleated foam cells, also enhances the binding of influenza A virus to neutrophil gran- whereas the alveolar type II cells are hyperplastic and contain giant ulocytes and promotes the neutrophil respiratory burst in response lamellar bodies. to the virus (11). SP-D binds to and induces aggregation of other SP-D is generally recognized as a molecule expressed in alve- microorganisms, such as Gram-negative bacteria (12) and the olar type II cells and Clara cells, but it has also been demonstrated fungi Cryptococcus neoformans and Aspergillus fumigatus (13, in mucus cells of the rat gastric mucosa (28), and extrapulmonary 14). SP-D binds directly to alveolar macrophages in the absence of expression has been detected in murine tissues (29). In this report, microbial ligands, thereby mediating the generation of oxygen rad- the extrapulmonary expression of human SP-D was investigated icals (15), and also acts as a potent chemotactic agents for phago- by RT-PCR and immunohistochemistry. SP-D was found to be cytes (16, 17). SP-D has been localized in endocytic vesicles and expressed in relation to mucosal surfaces in numerous glands and organs. *Department of Immunology and Microbiology, Institute of Medical Biology, Uni- versity of Southern Denmark, Odense University, Odense, Denmark; and †Statens Materials and Methods Serum Institut, Copenhagen, Denmark SDS-PAGE and Western blotting Received for publication July 15, 1999. Accepted for publication March 21, 2000. Electrophoresis was performed on 4–14% (w/v) polyacrylamide gradient The costs of publication of this article were defrayed in part by the payment of page gels with discontinuous buffers using the FAST system (Pharmacia, Pis- charges. This article must therefore be hereby marked advertisement in accordance cataway, NJ). Samples were reduced by heating to 100°C for 3 min with 40 with 18 U.S.C. Section 1734 solely to indicate this fact. mM DTT in 0.1 M Tris-HCl buffer, pH 8.0, containing 1.5% (w/v) SDS 1 This work was supported by the Danish Medical Research Council, Michaelsen and 5% (v/v) glycerol, and carboxamidated by the addition of iodoacet- Fonden, the Novo Nordisk Foundation, Fonden til Lægevidenskabens Fremme, Na- amide to 90 mM. Unreduced samples were heated in sample buffer with 90 tionalforeningens Fond, and the Benzon Foundation. mM iodoacetamide. After electrophoresis, proteins were electroblotted 2 Address correspondence and reprint requests to Dr. Uffe Holmskov, Immunology onto polyvinylidene difluoride membranes (Immobilon P, Millipore, and Microbiology, Institute of Medical Biology, University of Southern Denmark, Odense Bedford, MA). University, DK-5000 Odense, Denmark. E-mail address: [email protected] The membrane was incubated with primary Ab (monoclonal SP-D Ab, 3 Abbreviations used in this paper: SP-D, lung surfactant protein D; DMBT1, deleted 50 ng/ml) and secondary alkaline phosphatase-coupled rabbit anti-mouse in malignant brain tumors 1. Ig in 10 mM Tris-HCl, pH 7.4, containing 0.5 M NaCl, 15 mM NaN3, and 0.05% Copyright © 2000 by The American Association of Immunologists 0022-1767/00/$02.00 The Journal of Immunology 5867 FIGURE 1. RT-PCR analysis of SP-D expression in human tissues. Total mRNA (2 ␮g) from 19 different tissues were amplified, separated in 1.2% (w/v) agarose gel, blotted onto nylon membrane, and hybridized with either a human SP-D or a ␤-ac- tin oligonucleotide probe as de- scribed in Materials and Methods. (v/v) Tween 20 (polyoxyethylene sorbitan monolaurate, Merck-Schuchardt, Ho- were fixed in 4% formalin in 10 mM sodium phosphate buffer, pH 7.4, henbrunn, Germany). The membranes were washed and developed with containing 140 mM NaCl (PBS) for 24 h and then conventionally dehy- nitroblue tetrazolium and potassium 5-bromo-4-chloro-3-indolylphosphate. drated and embedded in paraffin. A biotin-streptavidin immunoperoxidase technique was used on paraffin Reverse-transcriptase PCR sections. Briefly, the paraffin sections were pretreated in 10 mM sodium Downloaded from citrate buffer, pH 6.0, in a microwave oven for three 5-min periods at 650 Total RNA was obtained from whole organs from various human tissues W. The sections were left in citrate buffer for 15 min; washed in 10 mM (Clontech, Palo Alto, CA). Two micrograms of total RNA were used for Tris-HCl, pH 7.2, containing 140 mM NaCl and 7.5 mM NaN (TBS); first-strand synthesis using the antisense SP-D primer, SP-DR1, 5Ј-TCA- 3 preincubated with 2% (w/v) BSA in TBS for 10 min; incubated for 30 min GAACTCGCAGACCA-3Ј. This sequence corresponds to nucleotides with Hyb 245-1, 5 ␮g/ml in TBS containing 1% (w/v) BSA; washed with 1282–1298 of the cDNA sequence of SP-D (2). The RNA was incubated TBS; incubated for 30 min with biotin-labeled goat anti-mouse Ig (Dako, in a volume of 20 ␮l with 20 U Moloney murine leukemia virus reverse Carpinteria, CA) diluted 1:200 in TBS; washed with TBS; incubated with http://www.jimmunol.org/ transcriptase (Stratagene, La Jolla, CA) at 37°C for 1 h. One-fourth of the HRP-coupled streptavidin (Dako) diluted 1:300 in TBS without NaN ; resulting cDNA was subjected to 40 cycles of PCR amplification in a 3 washed with TBS and water; incubated for 20 min with 0.04% 3-amino- volume of 30 ␮l with a denaturation temperature of 94°C for 30 s, anneal- 9-ethylcarbazole (Sigma, St.
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