EICOSANOID SYNTHESIS IN HUMAN PERITONEAL-MACROPHAGES STIMULATED WITH S-EPIDERMIDIS

Peritoneal macrophages isolated from CAPD patients phagocytozed S. epidermidis in a time dependent manner. Coincident with a maximum phagocytic uptake of 56% by 12 hours, there was secretion of a significant amount of neutral protease (1.37 ± 0.2 mg [3H]-casein degraded/106 cells, P = 0.05). In contrast to these delayed effects, coincubation of PMO with S. epidermidis resulted in a significant increase in both LTB4 and LTC4 synthesis above that of controls, with 6.33 ± 1.20 ng LTB4/106 cells (P < 0.01) and 2.06 ± 0.68 ng LTC4/106 cells (P = 0.014) being generated by three hours. The generation of these lipoxygenase products was both time and dose dependent, and the rapid production and release of the potently chemotactic LTB4 is consistent with the observed clinical response, where a rapid influx of PMN into the peritoneal cavity occurs during episodes of peritonitis, while the generation of LTC4 may contribute to the hyperemia and interstitial edema. In contrast, although there was a time dependent rise in cyclooxygenase product generation by unstimulated cells, a dose dependent inhibition of synthesis was clearly demonstrated when cells were incubated with bacteria, with a mean 40% reduction in generation of PGE2 and a mean 34% reduction in TXB2 generation (P = 0.01 and P < 0.025, respectively). It was demonstrated that the inhibition was not due to lack of available substrate and that the generation of eicosanoids was unrelated to phagocytosis, bacterial/PMO contact or bacterial surface characteristics. Instead, the observed effect of S. epidermidis on the PMO was attributable to a secreted bacterial product.