PROSTAGLANDIN AND FATTY-ACID MODULATION OF ESCHERICHIA-COLI O157 PHAGOCYTOSIS BY HUMAN MONOCYTIC CELLS

Phagocytosis by human monocytes is an important primary survival mecha nism particularly during bacterial infection. However, the processes t hat control the events and mediators involved in the activation of mon ocytes and their impact on the phagocytosis of bacteria are poorly und erstood. The effect of bacterial endotoxin, interleukin-1 beta (IL-1 b eta), fatty acids and prostaglandin E-2 (PGE(2)) on the phagocytosis o f fluoroscein isothiocyanate (FITC)-labelled Escherichia coil (O157) b y human blood monocytes and U937 cells was studied by flow cytometry. Endotoxin increased the phagocytosis of labelled bacteria by both mono cytes and U937 cells. IL-1 beta and the polyunsaturated fatty acids; d ihomo-gamma-linolenic and arachidonic acids also increased the phagocy tic activity of both monocytes and U937 cells. In contrast, PGE(2) sup pressed phagocytosis in a concentration-dependent manner. The cyclo-ox ygenase inhibitor, ketoprofen, further enhanced the increased phagocyt ic activity in the presence of endotoxin and interleukin-1 (IL-1) indi cating suppression by endogenous prostaglandins. This was confirmed by the data which showed that lipopolysaccharide (LPS) and IL-1 increase d PGE(2) release and ketoprofen inhibited release. Endotoxin and fatty acids increased IL-1 beta release also, whereas PGE(2) inhibited rele ase. The data suggest that phagocytic activity may be linked to change s in IL-1 levels. The data presented in this study also suggest that m onocyte phagocytosis in the course of bacterial infection would be alt ered during pathophysiological events which result in elevation of ext racellular fatty acids.