ACTIVATION OF NADPH OXIDASE IN HUMAN-NEUTROPHILS - SYNERGISM BETWEEN FMLP AND THE NEUTROPHIL PRODUCTS PAF AND LTB4

The induction of the respiratory burst in human neutrophils by combinations of fMLP [formylmethionylleucylphenylalanine] and either PAF [platelet-activating factor] or LTB4 [leukotriene B4] was studied. Pretreatment wiht PAF (0.0001 to 10 .mu.M), which by itself did not elicit the burst, greatly enhanced the rate and extent of fMLP-induced superoxide production. A synergism of a different kind was observed with the reversed stimulus sequence: Pretreatment with fMLP made the neutrophils capable of responding to PAF with superoxide production. A moderate enhancement of the fMLP response was also obtained following pretreatment with LTB4. The response of the cells to LTB4, however, was not influenced by fMLP, and no synergism was observed between the 2 neutrophil products PAF and LTB4. These results demonstrate a marked synergism between fMLP and PAF and suggest that PAF may function as an amplifier of the respiratory burst response of stimulated neutrophils.