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

Abstract

02 consumption resulting from interaction of Neisseria gonorrhoeae and human neutrophils represents a composite of 02 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 threefold increase in gonococcal 02 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 02 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°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°C. Lactate accumulation was inhibited by NaF and decreased temperature of incubation. Lactate at levels present in cell-free supernatant increased gonococcal 02 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 02 metabolism.

Aerobically Derived Lactate Stimulates Revascularization and Tissue Repair via Redox Mechanisms

“…via inflammation (8)) and where pO 2 can be independently controlled. To meet these requirements, we devised a Matrigel® implant model that shows no ability by itself to induce neovascularization but supports new vessel growth when made host to an angiogenic signal (10).…”

Defenses against Oxidative Stress inNeisseria gonorrhoeae: a System Tailored for a Challenging Environment

“…In support of the significance of nonoxidative killing, it has been shown that PMNs from people with chronic granulomatous disorder (NADPH oxidase deficient) had phagocytic killing capacities identical to PMNs from healthy donors (198) and that anaerobic PMNs kill as effectively as aerobic PMNs (46). N. gonor-rhoeae cells exposed to serum-or phagocyte-derived lactate have increased metabolism, including increased lactate dehydrogenase activity, and rapidly consume available molecular oxygen, reducing the ability of PMNs to mount an oxidative response (29)(30)(31)82). N. gonorrhoeae cells are also susceptible to the oxygen-independent components of PMN granules, including cathepsin G (45,197,(214)(215)(216)(217); reviewed in reference 218).…”

Mucosal infection with Neisseria gonorrhoeae. Bacterial adaptation and mucosal defenses.

“…However, the binding patterns are different between serum resistant and sensitive organisms (38 (49). Lactate is found in serum and is generated by phagocytes during aerobic glycolysis evoked by phagocytosis (50). The use of L(+)-lactate by gonococci is potentially important because of phenotypic changes that may occur through the use of this substrate (49), and because gonococci using L(+)-lactate demonstrate markedly accelerated competition for molecular oxygen (50).…”

“…Lactate is found in serum and is generated by phagocytes during aerobic glycolysis evoked by phagocytosis (50). The use of L(+)-lactate by gonococci is potentially important because of phenotypic changes that may occur through the use of this substrate (49), and because gonococci using L(+)-lactate demonstrate markedly accelerated competition for molecular oxygen (50). Indeed, through competition for molecular oxygen gonococci may prevent neutrophil generation of oxidants (see below, and Fig.…”

“…As discussed above, lack of association with neutrophils of Opa-gonococci, or selected Opa variants, may allow bacterial survival. Upregulation of gonococcal catalase production helps to defend against oxidative killing (63), as does aggressive competition for molecular 02 (50 …”