In response to complement anaphylatoxin peptides C3a and C5a, human vascular endothelial cells migrate and mediate the activation of B‐cells and polarization of T‐cells

The FASEB JournalVolume 34, Issue 6 p. 7540-7560 RESEARCH ARTICLEFree to Read In response to complement anaphylatoxin peptides C3a and C5a, human vascular endothelial cells migrate and mediate the activation of B-cells and polarization of T-cells Pooja Shivshankar, Pooja Shivshankar Research Center for Immunology and Autoimmune Diseases, Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USASearch for more papers by this authorYi-Dong Li, Yi-Dong Li Research Center for Immunology and Autoimmune Diseases, Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USASearch for more papers by this authorStacey L. Mueller-Ortiz, Stacey L. Mueller-Ortiz Research Center for Immunology and Autoimmune Diseases, Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USASearch for more papers by this authorRick A. Wetsel, Corresponding Author Rick A. Wetsel [email protected] Research Center for Immunology and Autoimmune Diseases, Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA Correspondence Rick A. Wetsel, Brown Foundation Institute of Molecular Medicine, 1825 Pressler Street, Suite 430A, Houston, TX 77030, USA Email: [email protected]Search for more papers by this author Pooja Shivshankar, Pooja Shivshankar Research Center for Immunology and Autoimmune Diseases, Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USASearch for more papers by this authorYi-Dong Li, Yi-Dong Li Research Center for Immunology and Autoimmune Diseases, Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USASearch for more papers by this authorStacey L. Mueller-Ortiz, Stacey L. Mueller-Ortiz Research Center for Immunology and Autoimmune Diseases, Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USASearch for more papers by this authorRick A. Wetsel, Corresponding Author Rick A. Wetsel [email protected] Research Center for Immunology and Autoimmune Diseases, Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA Correspondence Rick A. Wetsel, Brown Foundation Institute of Molecular Medicine, 1825 Pressler Street, Suite 430A, Houston, TX 77030, USA Email: [email protected]Search for more papers by this author First published: 17 April 2020 https://doi.org/10.1096/fj.201902397R Funding information This work was supported by a National Institutes of Health Public Service Grant RO1 AI025011 (to RAW). Support was also provided by the Hans J. Müller-Eberhard and Irma Gigli Distinguished Chair in Immunology Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract The vascular endothelium has been discovered in the past several years to be important in shaping the cellular immune response. During the immune response the vascular endothelium is constantly perturbed by biologically potent molecules, including the complement activation peptides, C3a and C5a. Despite the importance of C3a and C5a in inflammation and immunity, their role in modulating lymphocyte function via activation of vascular endothelial cells is unknown. Accordingly, we investigated the regulated expression of the C3a and C5a receptors (complement anaphylatoxin C3a receptor [C3aR] and complement anaphylatoxin C5a receptor 1 [C5aR1]) on human umbilical vascular endothelial cells (HUVECs) and examined how C3a or C5a activation of HUVECs affects the activation and polarization of lymphatic cells. Our findings demonstrated that C3a and C5a increase C3aR and C5aR1 expression by HUVECs as well as directing their cellular transmigration and spreading through transwell filters. Moreover, C3a- or C5a-stimulated endothelial cells: (1) caused activation of B-lymphoblasts with significant increase in Fas Ligand (CD95L) (FasL), CD69, and IL-R1 expression, and (2) skewed T-lymphoblast cells toward a Th1 subtype, (CD4+/CCR5+) that correlated with significant increase of IFN-γ. Collectively, these data indicate that C3a and C5a signaling is important in the activation and polarization of lymphocytes as they traffic through the vascular endothelium during the immune response. CONFLICT OF INTEREST The authors declare no conflicts of interest. Volume34, Issue6June 2020Pages 7540-7560 RelatedInformation