Mechanism of the activation of human phagocytes by cytokines and chemotactic factors

evidence for Ca²⁺-and protein kinase C-independent signaling pathways

Abstract

Cytokines (IL-1, TNF, G-CSF, GM-CSF, M-CSF, IL-3 and IFNγ), chemokines (IL-8, MCAF and others) and chemotactic factors (FMLP, C5a and PAF) stimulate respiratory burst activity in human neutrophils and/or monocytes via cell surface receptors specific for each agonist. Chemotactic factors and chemokines induce an increase in cytoplasmic free Ca²⁺ concentration, whereas cytokines other than chemokines do not. Cytokines do not induce activation of protein kinase C, and some of the responses triggered by chemotactic factors are also resistant to the inhibitors of protein kinase C.
Thus, the signaling pathways independent of Ca²⁺ and protein kinase C could be important in the activation of human phagocytes stimulated by the receptor-mediated agonists. One candidate for such pathway is tyrosine kinase and, in fact, we and other investigators found that cytokines and chemotactic factors induce tyrosine phosphorylation of 42-kDa microtubule-associated protein (MAP) kinase in a time course specific for each agonist in human neutrophils and/or monocytes.
So, MAP kinase pathway could be a central thema, though causal relationship between MAP kinase activation and functional activation is not clear. Among human phagocytes, mechanism of activation of macrophages await much further investigation.