{"id":3581,"date":"2022-02-07T18:07:22","date_gmt":"2022-02-07T18:07:22","guid":{"rendered":"http:\/\/wp.cov19longhaulfoundation.org\/?p=3581"},"modified":"2022-02-07T18:07:22","modified_gmt":"2022-02-07T18:07:22","slug":"the-spike-protein-of-sars-cov-2-induces-endothelial-inflammation-through-integrin-%ce%b15%ce%b21-and-nf-%ce%bab-signaling","status":"publish","type":"post","link":"https:\/\/cov19longhaulfoundation.org\/?p=3581","title":{"rendered":"The spike protein of SARS-CoV-2 induces endothelial inflammation through integrin \u03b15\u03b21 and NF-\u03baB signaling"},"content":{"rendered":"\n<h1 class=\"has-normal-font-size wp-block-heading\">Authors: <a href=\"https:\/\/www.jbc.org\/article\/S0021-9258(22)00135-1\/fulltext#\">Juan Pablo Robles<\/a>&nbsp;<a href=\"https:\/\/www.jbc.org\/article\/S0021-9258(22)00135-1\/fulltext#\"><sup>1<\/sup><\/a><a href=\"mailto:juanpabloroblesa@gmail.com\"><\/a><a href=\"https:\/\/www.jbc.org\/article\/S0021-9258(22)00135-1\/fulltext#\">Magdalena Zamora<\/a>&nbsp;<a href=\"https:\/\/www.jbc.org\/article\/S0021-9258(22)00135-1\/fulltext#\"><sup>1<\/sup>Elva Adan-CastroLourdes Siqueiros-MarquezGonzalo Martinez de la EscaleraCarmen Clapp<\/a><\/h1>\n\n\n\n<h2 class=\"has-normal-font-size wp-block-heading\">Open AccessDOI:<a href=\"https:\/\/doi.org\/10.1016\/j.jbc.2022.101695\">https:\/\/doi.org\/10.1016\/j.jbc.2022.101695<\/a><\/h2>\n\n\n\n<figure class=\"wp-block-image size-full is-style-default\"><img decoding=\"async\" src=\"http:\/\/wp.cov19longhaulfoundation.org\/wp-content\/uploads\/2022\/02\/JBClogo.png\" alt=\"\" class=\"wp-image-3582\"\/><\/figure>\n\n\n\n<p>Vascular endothelial cells (ECs) form a critical interface between blood and tissues that maintains whole-body homeostasis. In COVID-19, disruption of the EC barrier results in edema, vascular inflammation, and coagulation, hallmarks of this severe disease. However, the mechanisms by which ECs are dysregulated in COVID-19 are unclear. Here, we show that the spike protein of SARS-CoV-2 alone activates the EC inflammatory phenotype in a manner dependent on integrin \u237a5\u03b21 signaling. Incubation of human umbilical vein ECs with whole spike protein, its receptor-binding domain, or the integrin-binding tripeptide RGD induced the nuclear translocation of NF-\u03baB and subsequent expression of leukocyte adhesion molecules (VCAM1 and ICAM1), coagulation factors (TF and FVIII), proinflammatory cytokines (TNF\u237a, IL-1\u03b2, and IL-6), and ACE2, as well as the adhesion of peripheral blood leukocytes and hyperpermeability of the EC monolayer. In addition, inhibitors of integrin \u237a5\u03b21 activation prevented these effects. Furthermore, these vascular effects occur&nbsp;<em>in vivo<\/em>, as revealed by the intravenous administration of spike, which increased expression of ICAM1, VCAM1, CD45, TNF\u03b1, IL-1\u03b2, and IL-6 in the lung, liver, kidney, and eye, and the intravitreal injection of spike, which disrupted the barrier function of retinal capillaries. We suggest that the spike protein, through its RGD motif in the receptor-binding domain, binds to integrin \u237a5\u03b21 in ECs to activate the NF-\u03baB target gene expression programs responsible for vascular leakage and leukocyte adhesion. These findings uncover a new direct action of SARS-CoV-2 on EC dysfunction and introduce integrin \u237a5\u03b21 as a promising target for treating vascular inflammation in COVID-19.<\/p>\n\n\n\n<p>Click The Link Below For Full Details:<\/p>\n\n\n\n<p><a href=\"https:\/\/www.jbc.org\/action\/showPdf?pii=S0021-9258%2822%2900135-1\">https:\/\/www.jbc.org\/action\/showPdf?pii=S0021-9258%2822%2900135-1<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Authors: Juan Pablo Robles&nbsp;1Magdalena Zamora&nbsp;1Elva Adan-CastroLourdes Siqueiros-MarquezGonzalo Martinez de la EscaleraCarmen Clapp Open AccessDOI:https:\/\/doi.org\/10.1016\/j.jbc.2022.101695 Vascular endothelial cells (ECs) form a critical interface between blood and tissues that maintains whole-body homeostasis. [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":3587,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[770,144,541,576],"tags":[],"class_list":["post-3581","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-covid-spike-proteins","category-endothelium","category-spike-protein","category-thrombosis"],"_links":{"self":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/3581","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=3581"}],"version-history":[{"count":0,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/3581\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/media\/3587"}],"wp:attachment":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3581"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=3581"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=3581"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}