SUPPLEMENTAL L-ARGININE HCL AUGMENTS BACTERIAL PHAGOCYTOSIS IN HUMAN POLYMORPHONUCLEAR LEUKOCYTES

That L-arginine (L-Arg) augments the host response to acute bacterial sepsis suggests that this amino acid intervenes early in the immune re sponse, perhaps via the nitric oxide synthetase (NOS) pathway. The eff ect of L-Arg supplementation on in vitro phagocytosis of fluorescein-l abeled, heat-killed Staphylococcus aureus by peripheral blood neutroph ils (PMNs) from 12 normal human volunteers was studied. Separated PMNs were incubated for 2 h with labeled bacteria, with and without supple mental L-Arg, D-arginine, glycine, and/or the NOS inhibitors L-canavan ine, aminoguanidine, or L-N-G-nitroarginine methyl ester. PMNs were fi xed and extracellular fluorescence quenched with crystal violet. By fl ow cytometry and confocal microscopy, L-Arg supplementation was shown to result in a highly significant increase in PMN bacterial phagocytos is, the maximal effect being seen with L-Arg 380 mu M and falling off with higher concentrations. This augmentation was completely abrogated by NOS inhibitors in molar excess, but inhibitors alone did not suppr ess phagocytosis below that of unsupplemented controls. Neither D-argi nine nor glycine affected phagocytosis; the L-Arg effect was stereospe cific and not related to utilization of L-Arg as an energy source. L-A rg supplementation significantly enhances bacterial phagocytosis in hu man neutrophils, perhaps by effects on cytoskeletal phenomena, and thi s appears to be mediated through NOS activity. Phagocytosis by nonspec ific immune cells which intervene early in the response to sepsis is c ritically important, and beneficial effects of L-Arg on the clinical c ourse of sepsis may be due at least in part to augmentation of phagocy te function. (C) 1996 Wiley-Liss, Inc.