title: Blocking α5β1 Integrin Attenuates sCD40L-Mediated Platelet Activation.
abstract: The soluble form of CD40L (sCD40L) is a platelet-derived mediator that links inflammation, hemostasis, and vascular dysfunction. Indeed, blockade of CD40L by neutralizing antibodies or genetic disruption in mice prevents atherosclerosis and atherothrombosis. Until recently, it was believed that CD40 and αIIbβ3 were the only receptors on platelets responsible for binding sCD40L, leading to platelet activation and initiation of thrombotic events. Recent findings showed α5β1 integrin as a novel platelet sCD40L receptor, with an unknown function. For the first time, using anti-α5β1 blocking antibodies, we show that sCD40L/α5β1 interaction leads to platelet activation as evaluated in the human whole blood. Establishing α5β1 integrin's role in platelet activation, and therefore thrombosis will help further shed light on the etiology of thrombotic disease.
authors.affiliation: 1 Preclinical Development & Safety, Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Damir
authors.initials: D
authors.lastname: Simic
authors.affiliation: 1 Preclinical Development & Safety, Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Bogdan
authors.affiliation: 2 Biologics Discovery Sciences, Spring House, Janssen Research & Development, LLC, PA, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Teng
authors.affiliation: 1 Preclinical Development & Safety, Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Monicah
authors.initials: M
authors.lastname: Otieno
mesh_terms: D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001800:Blood Specimen Collection; D023201:CD40 Ligand / Q000378:metabolism*; D064368:Healthy Volunteers; D006801:Humans; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D012995:Solubility; D013927:Thrombosis / Q000209:etiology
chemical_list: D057134:Antibodies, Neutralizing; D039081:Integrin alpha5beta1; D023201:CD40 Ligand
keywords: CD40 ligand; and flow cytometry; platelet activation; α5β1 integrin