Leukocyte granule proteins mobilize innate host defenses and adaptive immune responses

Abstract

"... It is likely that the leukocyte granulations are in fact secretory products, which the cell dissolves and spreads to the environment as needed", Paul Ehrlich, 1900. Neutrophil granules have long been recognized as mediators of innate host defense. Newly discovered functions for individual granule proteins suggest that granule constituents may also participate in adaptive immune responses. Neutrophil granule-derived cathepsin G, azurocidin/CAP37 and alpha-defensins have been shown to be chemotactic for mononuclear cells and neutrophils. Analysis of the chemotactic activity of alpha-defensins shows that they induce CD45RA+ and CD8 T-lymphocyte cell migration at concentrations 10 to 100-fold below that required for direct bactericidal activity. Additionally, alpha and beta defensins form chemotactic gradients for immature dendritic cells. Recruiting immature dendritic cells to sites of infection is one way for neutrophil granule proteins to initiate adaptive immune responses. Granules found in other leukocytes such as mast cells also contain serine proteases, such as chymase, that are known to chemoattract neutrophils and mononuclear cells. Preliminary evidence suggests that exocytosis of granule-derived products from a variety of leukocytes can mobilize inflammatory cells and immunocytes. Thus, leukocyte granule-derived proteins, more rapidly than chemokines, can mobilize cells that mediate innate host defense and adaptive immunity.