Platelet interleukin-1α drives cerebrovascular inflammation
Open Access
- 29 April 2010
- journal article
- Published by American Society of Hematology in Blood
- Vol. 115 (17), 3632-3639
- https://doi.org/10.1182/blood-2009-11-252643
Abstract
White blood cell infiltration across an activated brain endothelium contributes to neurologic disease, including cerebral ischemia and multiple sclerosis. Identifying mechanisms of cerebrovascular activation is therefore critical to our understanding of brain disease. Platelet accumulation in microvessels of ischemic mouse brain was associated with endothelial activation in vivo. Mouse platelets expressed interleukin-1α (IL-1α), but not IL-1β, induced endothelial cell adhesion molecule expression (ICAM-1 and VCAM-1), and enhanced the release of CXC chemokine CXCL1 when incubated with primary cultures of brain endothelial cells from wild-type or IL-1α/β–deficient mice. A neutralizing antibody to IL-1α (but not IL-1β) or application of IL-1 receptor antagonist inhibited platelet-induced endothelial activation by more than 90%. Platelets from IL-1α/β–deficient mice did not induce expression of adhesion molecules in cerebrovascular endothelial cells and did not promote CXCL1 release in vitro. Conditioned medium from activated platelets induced an IL-1α–dependent activation of mouse brain endothelial cells and supported the transendothelial migration of neutrophils in vitro. Thus, we have identified platelets as a key source of IL-1α and propose that platelet activation of brain endothelium via IL-1α is a critical step for the entry of white blood cells, major contributors to inflammation-mediated injury in the brain.Keywords
This publication has 49 references indexed in Scilit:
- Inflammation and the neurovascular unit in the setting of focal cerebral ischemiaNeuroscience, 2009
- The Dynamics and Mechanisms of Interleukin‐1α and β Nuclear ImportTraffic, 2008
- A role for leukocyte-endothelial adhesion mechanisms in epilepsyNature Medicine, 2008
- Evidence of platelet activation in multiple sclerosisJournal of Neuroinflammation, 2008
- Human Brain Microvascular Endothelial Cells and Umbilical Vein Endothelial Cells Differentially Facilitate Leukocyte Recruitment and Utilize Chemokines for T Cell MigrationJournal of Immunology Research, 2008
- Endothelial-Specific Knockdown of Interleukin-1 (IL-1) Type 1 Receptor Differentially Alters CNS Responses to IL-1 Depending on Its Route of AdministrationJournal of Neuroscience, 2007
- Neuroinflammation and Both Cytotoxic and Vasogenic Edema Are Reduced in Interleukin-1 Type 1 Receptor-Deficient Mice Conferring NeuroprotectionStroke, 2005
- Interleukin-1 and neuronal injuryNature Reviews Immunology, 2005
- Inhibition of Platelet Adherence to Brain Microvasculature Protects against SeverePlasmodium bergheiMalariaInfection and Immunity, 2003
- A Critical Role of Platelet Adhesion in the Initiation of Atherosclerotic Lesion FormationThe Journal of Experimental Medicine, 2002