Consequences of hypoxia on polymorphonuclear microbicidal activity

In vitro and in vivo experimental research has largely demonstrated the deleterious effects of hypoxia on phagocytosis. In 1976, Hohn compared the bactericidal activity of cultures of Staphylococcus aureus exposed to pressures of oxygen ranging from 0 to 150 mmHg in the presence of normal human polymorphonuclear leukocytes (PMN's) and PMN's from children suffering of Chronic Granulomatous Disease (CGD)40. They observed that bactericidal activity in normal PMN's decreased when oxygen pressure dropped under 30 mmHg and this was only half the normal activity in pressures around 0 mmHg, reaching a level similar to that of CGD subjects (Figure 1.6-1). However, the decrease in bactericidal activity of the hypoxic PMN's was reversible when normal conditions of oxygenation were restored in the environment, while those of PMN's of CGD subjects were not. Hypoxia, which is the equivalent of a lack of substrate in terms of the oxidative burst phenomenon, has similar consequences to those of the NADPH oxidase enzyme deficit (i.e., CGD sufferers)40. In an hypoxic environment, other authors have also observed a decrease in the bactericidal activity of the PMN's against a number of bacteria commonly found in wounds and abscesses (i.e., Proteus vulgaris, Salmonella typhi murium, Klebsiella pneumoniae, Staphylococcus albus, Pseudomonas aeruginosa, Escherichia coli, etc)41-43. Hence, the production of free radicals by the PMN's is decreased by 90 % in an anaerobic environment when compared to a normoxic environment. Anaerobic conditions prevent the oxidative burst from occurring in vitro, causing an arrest in the production of free radicals in the lysosomes and thus stopping to oxygen-dependent bactericidal activity40.

In vivo, the extent of the decrease in bactericidal activity of the PMN's in hypoxic conditions has been shown on an experimental model in dogs involving skin and muscle-skin flaps inoculated with Staphylococcus aureus44'45. This work clearly showed how infectious necrotic lesions developed in hypoxic areas in pressures under 30 to 40mmHg. Radioactive marking of the PMN's confirmed that they continued to migrate but that their bactericidal activity in the hypoxic tissues was affected. Harris has shown how bactericidal activity against Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae decreased in the lungs of mice in hypoxic conditions46.

Figure 1.6-1. Effects of different pressures of oxygen on PMN's in normal subjects and subjects suffering chronic granulomatous disease (CGD) (bacteria : Staphylococcus aureus)
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