Functional Consequences of Phospholipase A2 Activation in Human Monocytes
- 1 January 1990
- book chapter
- Published by Springer Nature
- Vol. 279, 125-136
- https://doi.org/10.1007/978-1-4613-0651-1_8
Abstract
Human monocytes release arachidonic acid upon stimulation with a variety of soluble or particulate agents. These include: phorbol esters (i.e., 12-0-tetradecanoate phorbol-13-acetate, TPA), calcium ionophores (ionomycin), serum-treated zymosan (STZ) concanavalin A (Con A), and, to a minor degree, lipopolysaccharides (LPS). Protein Kinase C activation or increased intracellular Ca2+ are common features of the actions of most, if not all, of these stimuli. Prevention of PKC activation by the use of staurosporine or chelation of extracellular calcium by EGTA selectively impaired AA release, indicating that PLA2 may be regulated by either pathway concurrently. The generation of inositol phosphates and diacylglycerol by the action of phospholipase C, notably upon interaction with opsonized particles during phagocytosis, apparently constitutes the physiological correlate of stimulation via these agents. Release of arachidonic acid by the action of PLA2 or other phospholipid hydrolyzing enzymes leads directly to the formation of cyclooxygenase products. In the presence of markedly elevated calcium concentrations, 5-lipoxygenase (LO) is activated as well, leading to the formation and release of leukotrienes. Agents which stimulate AA release also initiate other monocyte functions, including generation of reactive oxygen intermediates and lymphokine release. This observation makes it tempting to implicate PLA2 activation in many aspects of monocyte physiology. However, no correlation with PLA2 activation and either superoxide or lymphokine release was found when multiple stimuli, including TPA, ionomycin, serum-treated zymosan, concanavalin A, or LPS, were compared simultaneously. Instead, our results indicate that PLA2 activation is regulated by the same mechanisms, including PKC activation and increased Ca2+, as are other enzymes which determine expression of monocyte function.This publication has 17 references indexed in Scilit:
- L-663,536 (MK-886) (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-dimethylpropanoic acid), a novel, orally active leukotriene biosynthesis inhibitorCanadian Journal of Physiology and Pharmacology, 1989
- LipocortinBiochemical Society Transactions, 1989
- Signal transduction in human monocytes: Relationship between superoxide production and the level of kinase C in the membraneJournal of Cellular Physiology, 1986
- Staurosporine, a potent inhibitor of phospholipidCa++dependent protein kinaseBiochemical and Biophysical Research Communications, 1986
- Intracellular Ca2+ requirements for zymosan-stimulated phosphoinositide hydrolysis in mouse peritoneal macrophagesBiochemical and Biophysical Research Communications, 1986
- Evidence for sequential signals in the induction of the arachidonic acid cascade in macrophages.The Journal of Experimental Medicine, 1986
- Human monocyte chemiluminescence triggered by IgG aggregates. Requirement of phospholipase activation and modulation by Fc receptor ligandsCellular Immunology, 1984
- Inositol trisphosphate and diacylglycerol as second messengersBiochemical Journal, 1984
- Superoxide anion and hydrogen peroxide production by chemically elicited peritoneal macrophages—Induction by multiple nonphagocytic stimuliCellular Immunology, 1981