Leukocyte granule proteins mobilize innate host defenses and adaptive immune responses

"...It is likely that the leukocyte granulations are in fact secretory prod ucts, which the cell dissolves and spreads to the environment as needed", P aul Ehrlich, 1900. Neutrophil granules have long been recognized as mediato rs of innate host defense. Newly discovered functions for individual granul e proteins suggest that granule constituents may also participate in adapti ve immune responses. Neutrophil granule-derived cathepsin G, azurocidin/CAP 37 and alpha-defensins have been shown to be chemotactic for mononuclear ce lls and neutrophils. Analysis of the chemotactic activity of alpha-defensin s shows that they induce CD45RA(+) and CD8 T-lymphocyte cell migration at c oncentrations 10 to 100-fold below that required for direct bactericidal ac tivity. Additionally, alpha and beta defensins form chemotactic gradients f or immature dendritic cells. Recruiting immature dendritic cells to sites o f infection is one way for neutrophil granule proteins to initiate adaptive immune responses. Granules found in other leukocytes such as mast cells al so contain serine proteases, such as chymase, that are known to chemoattrac t neutrophils and mononuclear cells. Preliminary evidence suggests that exo cytosis of granule-derived products from a variety of leukocytes can mobili ze inflammatory cells and immunocytes. Thus, leukocyte granule-derived prot eins, more rapidly than chemokines, can mobilize cells that mediate innate host defense and adaptive immunity.