Granulocyte activation. Biochemical events associated with the mobilization of calcium

The past few years have seen a significant refinement in our understanding of the mechanism of activation of granulocytes. The involvement of surface receptors and the role of calcium as second messenger have been further supported by recent data. However, with the exception of the unexamined potential role of ITP, all the previous hypotheses attempting to provide a biochemical basis for the transduction mechanisms involved in calcium mobilization have either been dismissed or at least been seriously weakened by lack of experimental support. A particularly glaring example of the work that still needs to be done is the near total lack of knowledge about stimuli-induced changes in the physical properties of the plasma membrane of these cells and of the biochemical targets of the raised levels of cytoplasmic calcium (e.g. protein kinases). Glimpses into the nature of the calcium-independent pathway of neutrophil activation have been provided by phorbol esters. The modulatory nature of the role of cyclic mucleotides appears to have been established, its biochemical basis, however, is unknown. The description of the dynamic nature of the neutrophils' cytoskeletal structures should lay the foundation of the understanding of the regulation of the neutrophils' force generating system, the structure(s) ultimately responsible for the expression of the critical granulocyte functions of locomotion, phagocytosis, and granule fusion.