Extracellular pH affects inflammatory cell production of superoxide and nitric oxide

Abstract

Previous research has described how high cellular metabolism creates an acidic environment in inflammatory cells during respiratory burst. The aim of our work was to describe the acid-base dependence of exudate in superoxide (O2.-) and nitric oxide (NO.) generation by inflammatory cells from a carrageenan-granuloma. Although the carrageenan solution was alkaline (pH 7.74 when equilibrated with air) the exudate showed an acidification that stabilised at around 7 units of pH. A notable hypercapnia, but not hypoxia, was found in the exudate at up to 24 h. The effect of extracellular acidosis on O2.- and NO. production by inflammatory cells was also studied. The maximum O2.- production and the lowest levels of NO. were found at pH 7, which was closer to the pH of the granuloma-pouch. These results suggest that experiments with inflammatory cells ex vivo should be carried out at an identical pH to that found in vivo in order to reproduce the physiological mechanisms of free radical generation during inflammatory processes.

Oxidant activity in skeletal muscle fibers is influenced by temperature, CO2level, and muscle-derived nitric oxide

“…Via these and related pathways, CO 2 can undergo electron exchange reactions to form carbonate radicals (28). Dissolved CO 2 also influences the pH of biological systems, as observed in this study, and extracellular acidosis increases cellular production of both ROS and NO (8). Studies in nonmuscle cell types are conflicted about the net effect of CO 2 -mediated reactions, which are reported both to exaggerate NO-mediated injury (23,37) and protect against nitrosative and oxidative stress (9,12,52).…”

“…CO 2 and bicarbonate react directly with NO derivatives (3,52) and undergo electron exchange reactions to form carbonate radicals (28). Dissolved CO 2 also promotes acidosis in biological systems, stimulating cellular production of ROS and NO (8). Studies in nonmuscle cell types are conflicted about the net effect of CO 2 -mediated reactions that appear to either promote (23,37) or protect against (9,12,52) oxidative and nitrosative stress.…”

Impact of Systemic Acidosis on the Development of Malignant Ventricular Arrhythmias After Reperfusion Therapy for ST-Elevation Myocardial Infarction

“…27 Moreover, extracellular acidosis reportedly increases superoxide production by inflammatory cells. 28 Therefore, it is possible that systemic acidosis amplifies the post-infarction inflammatory response, thereby rendering the infarcted myocardium more susceptible to the development of VT/VF. Activation of neutrophils and platelets has been implicated in the endothelial dysfunction and tissue damage associated with ischemia -reperfusion, 24 as evidenced by the protective effects of neutrophil depletion or specific blockade of neutrophil or platelet adhesion molecules in animal models of ischemia -reperfusion.…”

Systemic Acidosis in Acute Myocardial Ischemia

“…10 Extracellular acidosis can also cause a hyper oxidative state through increased production of superoxide from inflammatory cells. 11 Additionally, acidosis itself may directly influence electrical activity. Increased extracellular protons increase intracellular Na + and Ca 2+ through the actions of the Na + -H + and Na + -Ca 2+ exchangers, and then the induced Ca 2+ overload may shorten the effective refractory period 12 and may also exaggerate the occurrence of reperfusion arrhythmia.…”