Activation of human polymorphonuclear neutrophilic granulocytes by immuno-modulating cytokines: an ultrastructural study.

Activated granulocytes play an important role in the propagation of inflammatory reactions and are capable of mediating tissue damage by the release of reactive oxygen species and lysosomal contents. Cytokines produced by immunocompetent and other cells were recently suggested to influence granulocyte functions. Therefore, in the present study, we investigated the effect of relevant immuno-modulating cytokines on isolated human granulocytes by ultrastructural criteria: scanning and transmission electron microscopy, ultrastructural detection of H2O2. The following recombinant human cytokines were tested: tumor necrosis factor (TNF), lymphotoxin (LT), GM-CSF, M-CSF, G-CSF, interleukin 1 (IL 1) alpha and beta, IL 2, IL 3, IL 4, IL 6, interferon (IFN)-alpha and gamma. Only TNF, LT, GM-CSF and IL 3 (at high concentrations) induced significant morphological changes (increased adherence to plastic layers, typical polarization, development of intracellular vesicles) and production of H2O2. None of the other cytokines tested induced any detectable effect on isolated granulocytes even at unphysiological concentrations. The results clearly demonstrate that only certain cytokines are capable of influencing granulocytes. Release of these mediators represents a specific signal for granulocyte activation in inflammatory disease states.