Diverse Effects of Cytochalasin B on Priming and Triggering the Respiratory Burst Activity in Human Neutrophils and Monocytes

Abstract

Cytochalasin B, despite its potent enhancing effect on superoxide (O₂ ^-) release triggered by N-formyl-methionyl-leucyl-phenylalanine (FMLP) and many other agonists, significantly inhibited O₂ ^- release triggered by interleukin 8 (IL-8) and platelet-activating factor in human neutrophils. Cytochalasin B also enhanced changes in membrane potential stimulated by FMLP but inhibited those stimulated by IL-8. Using IL-8 as a triggering agonist, we found that the priming effect of tumor necrosis factor (TNF) and granulocyte-macrophage colony—stimulating factor (GM-CSF) on O₂ ^- release was slightly but significantly potentiated by cytochalasin B. O^{2 -} release triggered by TNF and GM-CSF was completely abolished by cytochalasin B. In contrast to these diverse effects of cytochalasin B on O₂ ^- release, changes in cytoplasmic pH stimulated by FMLP, IL-8, TNF, and GM-CSF were not or were only minimally affected by cytochalasin B. Unlike human neutrophils, human monocytes stimulated by FMLP showed inhibition of^{2 -} release and changes in membrane potential in response to cytochalasin B, and the priming effect of TNF and GM-CSF on^{2 -} release in human monocytes was completely abolished by cytochalasin B.These findings indicate the diverse effects of cytochalasin B on phagocytes and suggest distinct regulatory mechanisms according to the functions, agonists, and cell types.