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Amnion: Implications for Human Pregnancy Surfactant Protein-A as an Anti-Inflammatory Component in the Amnion: Implications for Human Pregnancy This information is current as Deug-Chan Lee, Roberto Romero, Chong Jai Kim, of September 26, 2021. Tinnakorn Chaiworapongsa, Adi L. Tarca, JoonHo Lee, Yeon-Lim Suh, Shali Mazaki-Tovi, Edi Vaisbuch, Pooja Mittal, Sorin Draghici, Offer Erez, Juan Pedro Kusanovic, Sonia S. Hassan and Jung-Sun Kim J Immunol 2010; 184:6479-6491; Prepublished online 3 May Downloaded from 2010; doi: 10.4049/jimmunol.0903867 http://www.jimmunol.org/content/184/11/6479 http://www.jimmunol.org/ References This article cites 52 articles, 9 of which you can access for free at: http://www.jimmunol.org/content/184/11/6479.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 26, 2021 • No Triage! Every submission reviewed by practicing scientists • 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 © 2010 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Surfactant Protein-A as an Anti-Inflammatory Component in the Amnion: Implications for Human Pregnancy Deug-Chan Lee,* Roberto Romero,*,†,‡,1 Chong Jai Kim,*,x Tinnakorn Chaiworapongsa,*,† Adi L. Tarca,*,‡,{ JoonHo Lee,* Yeon-Lim Suh,‖ Shali Mazaki-Tovi,*,† Edi Vaisbuch,*,† Pooja Mittal,*,† Sorin Draghici,{ Offer Erez,*,† Juan Pedro Kusanovic,*,† Sonia S. Hassan,*,† and Jung-Sun Kim*,x,‖,1 The mechanism of mouse parturition is thought to involve myometrial infiltration by amniotic fluid (AF) macrophages, activated by surfactant protein-A (SP-A). In humans, the concentration of AF SP-A decreases during labor, and no fetal macrophages are found in the myometrium after labor. Therefore, it appears that the mechanisms of labor in mice and humans are different. We investigated a potential role for SP-A in human pregnancy and parturition by examining SP-A expression patterns in AF and Downloaded from amnion. High molecular mass (>250 kDa) oligomeric SP-A was increased in AF with advancing gestation. Interestingly, these oligomers were more abundant in placental amnion before labor at term, while they increased primarily in reflected amnion during labor (p , 0.05). Immunoblotting showed a binding of high molecular mass SP-A in AF to amnion. In C57BL/6 mice, oligomeric SP-Awas also readily detected in AF from E15 onwards, but not in amnion. Macrophage density in mice myometrium did not change with advancing gestational age. Microarray analysis of human amnion explants incubated with SP-A revealed a molecular signature b of inhibited cytokine–cytokine receptor interaction with downregulation of IL-1 , CXCL2, and CXCL5 mRNA expression. The http://www.jimmunol.org/ findings in this study strongly suggest that SP-A signals amniotic anti-inflammatory response via AF during pregnancy. We propose that an SP-A interaction among AF, placental amnion, and reflected amnion is a unique mechanism for immunoregulation in human pregnancy akin to that established in lung biology. However, AF SP-A and fetal macrophages by themselves do not seem to be exclusive effectors of parturition in humans. The Journal of Immunology, 2010, 184: 6479–6491. uman spontaneous labor at term has a prominent proin- rioamniotic membranes. The amnion is in direct contact with the flammatory molecular signature in the chorioamniotic amniotic fluid and plays pivotal roles in the induction of labor by H membranes, particularly in the amnion (1, 2). This producing PGs and in delivery by membrane rupture (4). by guest on September 26, 2021 strongly suggests that human parturition has a physiologic in- Recently, we demonstrated that the human amnion is biologically flammatory and immunologic component, and also that the mole- compartmentalized into the placental amnion (amnion overlying cules that modulate amniotic proinflammatory responses play the placental disc) and the reflected amnion (amnion of the extrap- important roles in parturition. The amnion is a large mucosal sur- lacental chorioamniotic membranes). Of note, the labor-associated face stretched across the intrauterine surface, which reaches up proinflammatory response was a more prominent feature in the to 1,876 6 307 cm2 at term (3), and is the inner layer of the cho- placental amnion rather than in the reflected amnion (2). Previous studies have shown that inflammation activates amniotic biologic cascades associated with human labor. For example, proin- *Perinatology Research Branch, Department of Health and Human Services, Eunice flammatory cytokines IL-1 and TNF-a stimulated the production of Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; †Department of Obstetrics and Gynecology, ‡Center for Molecular PGE2 and induced cyclooxygenase-2 expression in the amnion (5, Medicine and Genetics, xDepartment of Pathology, Wayne State University School of 6). IL-1b and TNF-a increased IL-8 expression in the amnion cells Medicine; and {Department of Computer Science, Wayne State University, Detroit, MI ‖ (7). Moreover, intra-amniotic infection is the leading identifiable 48201; and Department of Pathology, Sungkyunkwan University School of Medicine, Seoul, Korea cause of preterm labor and delivery (8). During pregnancy, the bio- 1R.R. and J.-S.K. are co-senior authors. chemical composition of amniotic fluid changes as gestational age Received for publication December 2, 2009. Accepted for publication March 26, advances, and this could have an effect on the biology of the 2010. amnion. Conversely, the molecules produced by the amnion could This work was supported by the Perinatology Research Branch, Division of Intra- change their amniotic fluid concentrations. In this context, it is rea- mural Research, Department of Health and Human Services, Eunice Kennedy Shriver sonable to expect that a certain molecule, whose amniotic fluid National Institute of Child Health and Human Development, National Institutes of Health. concentration changes with progression of gestation and modulates amniotic inflammatory responses, plays an important role in human Address correspondence and reprint requests to Dr. Jung-Sun Kim, Department of Pathology, Wayne State University School of Medicine, Hutzel Women’s Hospital, pregnancy and parturition. 3990 John R, 4 Brush North, Room 4606, Detroit, MI 48201. E-mail address: Surfactant protein-A (SP-A) is a C-type lectin encoded by [email protected] SFTPA1 and SFTPA2 (9, 10), with a triple helical collagen region Abbreviations used in this paper: AB, ammonium bicarbonate; ACN, acetonitrile; AF, on the N-terminus and a carbohydrate recognition domain on the amniotic fluid; CRT, calreticulin; E, epithelial layer; GP, goat polyclonal; KEGG, Kyoto Encyclopedia of Genes and Genomes; LC-MS/MS, liquid chromatography- C terminus (11, 12). It is expressed by both the lung and the cho- tandem mass spectrometry; M, mesodermal layer; MM, mouse monoclonal; PA, pla- rioamniotic membranes (13–16). SP-A characteristically shows cental amnion; pI, isoelectronic point; RA, reflected amnion; RP, rabbit polyclonal; SIRPa, signal-regulatory protein a; SPIA, signaling pathway impact analysis; SP-A, a marked increase in the amniotic fluid with advancing gestational surfactant protein-A; TIL, term in labor; TNL, at term not in labor. age, and this is taken as an indicator of fetal lung maturity (17). www.jimmunol.org/cgi/doi/10.4049/jimmunol.0903867 6480 AMNIOTIC SP-A IN PREGNANCY Because its concentration sharply increases during the third trimester an animal facility under pathogen-free conditions. Mice were sacrificed on [compared with that of SP-D (18)], SP-A is an attractive candidate to E13, E15, E17, and E19. Fetal uterine, placental tissues, and amniotic fluid control human parturition because it would link fetal maturity with were collected. the onset of labor. Indeed, intra-amniotic administration of SP-Awas Immunoblotting shown to induce parturition in mice, and treatment with a neutralizing Proteins were extracted from liquid nitrogen-pulverized amnion, fetal lung Ab prolonged gestation in that species. Therefore, it has been pro- tissue, or cell pellets using radioimmunoprecipitation lysis buffer (Sigma- posed that activation of fetal amniotic fluid macrophages by SP-A and Aldrich, St. Louis, MO) containing a proteinase inhibitor mixture (Roche, their subsequent migration into the maternal myometrium are key Basel, Switzerland). Protein lysates underwent electrophoresis in 4–15% events for spontaneous parturition in mice. The injection of neutral- gradient SDS-PAGE (Bio-Rad, Hercules, CA) under reducing or nonreduc- ing conditions and then electroblotted onto polyvinylidene difluoride mem- izing anti–SP-A Ab into the amniotic cavity delayed mouse parturi- branes (GE Healthcare Bio-Sciences, Piscataway, NJ).After blocking for 1 h tion (19, 20). However, fetal macrophages have not been found in the with 5% nonfat dry milk in TBS containing 0.1% Tween 20 (0.1% TBS-T), the
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