IN-VITRO EFFECTS OF GM-CSF ON MATURE PERIPHERAL-BLOOD NEUTROPHILS

GM-CSF can play a crucial role in regulating the neutrophil-mediated i nflammatory response. This growth factor is a proliferative stimulus f or bone marrow neutrophil stem cell precursors and has at least 3 impo rtant roles in regulating neutrophil-mediated immunity: a) a direct ef fect on the proliferation and development of neutrophil progenitors; b ) synergistic activity with other haemopoietic growth factors; c) stim ulation of the functional activity of mature neutrophils. The producti on of GM-CSF may be triggered directly by exogenous factors such as an tigens and endotoxins, or indirectly through the release of cytokines by a variety of cells including lymphocytes, activated macrophages and endothelial cells exposed to products of mononuclear phagocytes. Such production of GM-CSF may serve to quickly release mature neutrophils from the bone marrow in response to infections. Moreover, enhancement of the function of mature neutrophils may also augment their ability t o migrate to infective sites and then phagocytose and kill pathogens. Increased expression of CD11b/CD18 may play a fundamental part in this mechanism because this receptor is essential for the adhesion of neut rophils to the endothelium. Both phagocytosis and oxidative burst acti vity increase as a result of the action of GM-CSF and the increased ex pression of complement- and Fc-receptors can augment opsono-phago-cyto sis. A futher level of neutrophil up-regulation occurs by increasing t he functional life span of neutrophils by GM-CSF. Thus, by delaying ne utrophil apoptosis, GM-CSF greatly extends the time over which neutrop hils may function at inflammatory sites. GM-CSF can thus exert a varie ty of important regulatory controls of neutrophil function during bact erial infections. Both the number and the functional status of neutrop hils is highly regulated by GM-CSF. It is also possible that GM-CSF pr oduced within localised sites of acute inflammation or infection may a ttract, trap and then activate neutrophils within this site.