Leukocyte adhesion dynamics in shear flow

Abstract

Of the white blood cells that traverse the circulation, the polymorphonuclear leukocytes commonly called neutrophils, are the most numerous, numbering approximately 5000 per microliter of blood. In a sense, these cells are the emergency response unit within the body's circulatory highway since they are the first to be recruited at sites of tissue trauma, infection, or inflammation. The chief function of neutrophils is the capture, phagocytosis, and degradation of foreign invaders. To carry out this critical function, neutrophils sense infection via chemotactic receptors that trigger cellular activation upon ligation of as few as 10-100 bacterial or chemokine peptides. Despite this acute sensitivity to stimuli, neutrophils circulate in healthy individuals largely in a passive state, with a very low efficiency of capture and arrest on quiescent endothelium. Here, we define the efficiency as the fraction of all cells passing by a given length of vessel wall that is captured and achieves firm adhesion. Within seconds of chemotactic signaling, adhesion molecules expressed on the plasma membrane of neutrophils are activated and a rapid boost in the efficiency of stable adhesion is detected. This occurs for both homotypic neutrophil-neutrophil adhesion and neutrophil capture and adhesion on inflamed endothelium. With such large numbers of circulating neutrophils, and with their inherent capability to rapidly adhere to postcapillary venular endothelium, the body has evolved a diverse set of mechanisms to regulate the inflammatory cascade that begins with intracellular signaling and leads to cell arrest and extravasation at sites of tissue insult. In this article we will focus on the interplay between particle-fluid dynamics that involve the shear and normal forces that transport cells transversely and axially within the vessel, and the activation and interaction of adhesion molecules that involve receptor-ligand bond formation that enables the neutrophils to resist wall shear stress and adhere to specific sites of inflammation.