John M. Harlan, MD
Professor, Department of Medicine
Inflammation and Vascular Biology: Leukocyte adherence to endothelium is a critical event in host defense and repair, but may also contribute to the pathogenesis of vascular and tissue injury in inflammatory and immune disorders. Adhesive interactions between circulating leukocytes and the vessel wall involve a cascade of events beginning with low-affinity adhesion manifested by rolling under conditions of flow, subsequent firm adhesion, and finally diapedesis between endothelial cells (EC) and migration to the extravascular site of inflammation or immune reaction. Using cell and molecular biology techniques and gene-targeted mice, our current studies examine: (1) the regulation of leukocyte integrin receptor avidity by high-density ligand and cyclin-dependent kinases and 2) the role of leukocyte VLA-4 integrin in the progression of advanced atherosclerosis in murine models. Recent studies also examine the mechanisms and consequences of EC or leukocyte apoptosis during inflammatory Ostress1. These studies involve in vitro investigation of the role of apoptotic signaling pathways in EC and leukocyte activation. Transgenic and gene-targeted mice are used to elucidate the contribution of apoptosis in disease models of ischemia-reperfusion injury and sepsis.