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 response, perhaps via the nitric oxide synthetase (NOS) pathway. The effect of L-Arg supplementation on in vitro phagocytosis of fluorescein-labeled, heat-killed Staphylococcus aureus by peripheral blood neutrophils (PMNs) from 12 normal human volunteers was studied. Separated PMNs were incubated for 2 h with labeled bacteria, with and without supplemental L-Arg, D-arginine, glycine, and/or the NOS inhibitors L-canavanine, aminoguanidine, or L-NG-nitroarginine methyl ester. PMNs were fixed and extracellular fluorescence quenched with crystal violet. By flow cytometry and confocal microscopy, L-Arg supplementation was shown to result in a highly significant increase in PMN bacterial phagocytosis, the maximal effect being seen with L-Arg 380 microM and falling off with higher concentrations. This augmentation was completely abrogated by NOS inhibitors in molar excess, but inhibitors alone did not suppress phagocytosis below that of unsupplemented controls. Neither D-arginine nor glycine affected phagocytosis; the L-Arg effect was stereospecific and not related to utilization of L-Arg as an energy source. L-Arg supplementation significantly enhances bacterial phagocytosis in human neutrophils, perhaps by effects on cytoskeletal phenomena, and this appears to be mediated through NOS activity. Phagocytosis by nonspecific immune cells which intervene early in the response to sepsis is critically important, and beneficial effects of L-Arg on the clinical course of sepsis may be due at least in part to augmentation of phagocyte function.
Moffat
F L
FL
Veterans Administration Medical Center, Miami, Florida 33136, USA.
Han
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T
Li
Z M
ZM
Peck
M D
MD
Jy
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W
Ahn
Y S
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Chu
A J
AJ
Bourguignon
L Y
LY
D001120:Arginine / Q000494:pharmacology*; D002478:Cells, Cultured; D002956:Citrulline / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010587:Phagocytosis / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000276:immunology
D004791:Enzyme Inhibitors; D002956:Citrulline; D001120:Arginine; D019001:Nitric Oxide Synthase