Phagocyte-derived lactate stimulates oxygen consumption by Neisseria gonorrhoeae. An unrecognized aspect of the oxygen metabolism of phagocytosis.

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Abstract

O2 consumption resulting from interaction of Neisseria gonorrhoeae and human neutrophils represents a composite of O2 consumed by the two cell systems. Experiments studying the relative contribution of each system suggested the possibility that gonococci increased their metabolic activity in response to interaction with neutrophils. This hypothesis was confirmed by demonstrating that undifferentiated HL-60 cells, which are unable to undergo a respiratory burst, induce a two- to three-fold increase in gonococcal O2 consumption. Gonococcal capacity to adhere to HL-60 cells did not correlate with extent of metabolic stimulation. Stimulatory activity was demonstrable in cell-free supernatant from neutrophils or HL-60 cells, and increased with duration of incubation. Supernatant applied to a G-15 Sephadex column yielded fractions that stimulated gonococcal O2 consumption. Elution profiles were similar for HL-60 cells, neutrophils, and a stimulatory factor previously isolated from pooled human serum. This stimulatory factor(s) failed to adhere to DEAE or C-18 HPLC columns. Stimulatory activity release from myeloid cells was inhibited by incubation at 4 degrees C or in the presence of NaF, indicating a critical role for glucose metabolism. Lactate, the principal product of resting neutrophil glucose catabolism, was demonstrable in cell-free supernatants after incubation at 37 degrees C. Lactate accumulation was inhibited by NaF and decreased temperature of incubation. Lactate at levels present in cell-free supernatant increased gonococcal O2 consumption twofold and restored stimulatory activity to dialyzed serum. Live, but not heat-killed gonococci eliminated lactate released from neutrophils during phagocytosis. Gonococci are able to utilize host-derived lactate to enhance their rate of O2 metabolism.

Authors

B E Britigan, D Klapper, T Svendsen, M S Cohen