Grant: Project Grant

The innate immune system plays a critical component of initial host defense. The recruitment of immune cells to sites of infection, immune reaction or injury is complex and requires a multistep adhesion cascade between the leukocytes (white blood cells) and the endothelial cells that line the vasculature. The classic paradigm for leukocyte recruitment involves the adhesive tethering, rolling followed by firm adhesion on the activated vasculature wall and involves the timely activation of the integrin and selectin families of adhesion receptors. Although this paradigm does hold true for a number of organs there is an increasing number of exceptions including the liver and lung microvasculature where the integrins and selectins play a small role if any. We and others have contributed to an evolving paradigm change in the identification of new organ-specific inflammatory molecules that mediate leukocyte activation and recruitment in different organs. Herein, we provide evidence that a specific molecule known as DPEP1 acts as a physical adhesion receptor for a specific type of white blood cell called neutrophils within the liver and lung blood vessels after stimulation with a bacterial component known as LPS. DPEP1 represents the first major adhesion receptor identified on lung endothelium. We propose that DPEP1 be added to the growing list of non-classical adhesion molecules, and accordingly represents a novel target for anti-inflammatory therapy for diseases of the lungs where acute and chronic inflammation is involved in the pathogenesis.