Figure 4.

A2M and neutrophil function. A2M* aids neutrophils through stimulation of their capacity to bind to endothelial cells (1), to migrate (2) and to phagocytose and kill pathogens (3). For example, the chemotactic potential of neutrophils is increased in the presence of A2M* by reducing LPS-induced G-protein-coupled receptor kinase 2 (GRK2) expression, which subsequently results in increased C-X-C motif chemokine receptor 2 (CXCR2) expression and increased neutrophil migration towards IL-8 (2). A2M* also induces CD11b in neutrophils challenged with LPS, thereby increasing the interaction with ICAM-1 and aiding neutrophil adhesion to the vascular endothelium (1). A2M* augments phagocytosis and bacterial killing by neutrophils, possibly through interaction with LRP-1 (4). Finally, A2M can inhibit all major proteases secreted by neutrophils and reduce their proteolytic activity against large substrates (5). However, in the presence of reactive oxygen species (ROS), such as hypochlorite, A2M dissociates thereby switching its activity from protease inhibition to an extracellular chaperone and cytokine carrier (6).