Regulation of monocyte oxidative metabolism: chemotactic factor enhancement of superoxide release, hydroxyl radical generation, and chemiluminescence.

Human peripheral blood mononuclear cells exposed to the synthetic chemotactic factor n-formyl-methionyl-leucyl-phenylalanine (FMLP) were enhanced in their ability to generate superoxide anion (O-2), hydroxyl radical (OH.), and chemiluminescence when later exposed to phorbol myristate acetate (PMA). When compared to oxidative responses of cells treated with PMA alone, the degree of enhancement by pretreatment with FMLP was 1.85-fold for O-2 generation, 1.73-fold for OH. production, and 1.34-fold for chemiluminescence. Similarly, pretreatment of mononuclear leukocytes with 5% zymosan-activated serum also enhanced subsequent oxidative responses of cells exposed to PMA. FMLP did not enhance subsequent O-2 release or chemiluminescence by mononuclear leukocytes stimulated by opsonized zymosan or 20 mM sodium fluoride (F-), demonstrating that the O-2 generating system of monocytes stimulated by phagocytosis or F- is not susceptible to chemotactic factor regulation in a manner similar to the system stimulated by PMA. The latter system, like that of neutrophils, is susceptible to regulation by cellular processes activated during an initial encounter with chemoattractants. These processes may provide a mechanism to amplify oxidative responses at sites of infection or inflammation, leading to enhanced efficiency of microbicidal activity or increased tissue damage in vivo.