Two Distinxt Apoptotic Pathway in Human Monocytes Mediated by IL-4 and Fas

Um, Hong Duck

Abstract

Apoptosis has ernerged as a key mechanism for regulating the number of leukocytes at sites of inflammation. Besides withdrawal of inflammatory stimuli, apoptosis of human monocytes can be directly triggered through two cell surface molecules, Fas and the IL-4 receptor. In contrast to Fas-mediated death which utilizes reactive oxygen intermediates (ROI) as instruments of death, IL-4-induced apoptosis of monocytes was neither blocked by antioxidants, nor accompanied by elevation of cellular ROI. Moreover, PMA which upregulates protein kinase C (PKC) inhibited IL-4-, but not Fas-mediated death. These data define a ROl-dependent, PKC-resistant Fas pathway, and a ROl-independent, PKC-susceptible IL-4 pathway of apoptosis. Monocyte apoptosis triggered by depletion of inflammatory mediators resembles the IL-4 pathway. Within the context of an inflammatory site, monocyte accumulation and depletion may be susceptible to manipulation through these pathways.