Hypercapnia Inhibits Autophagy and Bacterial Killing in Human Macrophages by Increasing Expression of Bcl-2 and Bcl-xL

摘要: Hypercapnia, the elevation of CO2 in blood and tissue, commonly develops patients with advanced lung disease severe pulmonary infections, it is associated high mortality. We previously reported that hypercapnia alters expression host defense genes, inhibits phagocytosis, increases mortality Pseudomonas pneumonia mice. However, effect on autophagy, a conserved process by which cells sequester degrade proteins damaged organelles also plays key role antimicrobial pathogen clearance, has not been examined. In present study we show autophagy induced starvation, rapamycin, LPS, heat-killed bacteria, live bacteria human macrophage. Inhibition elevated was attributable to acidosis. Hypercapnia reduced macrophage killing aeruginosa. Moreover, Bcl-2 Bcl-xL, antiapoptotic factors negatively regulate blocking Beclin 1, an essential component initiation complex. Furthermore, small interfering RNA targeting Bcl-xL molecule Z36, blocks binding prevented hypercapnic inhibition bacterial killing. These results suggest Bcl-2/Bcl-xL-Beclin 1 interaction may hold promise for ameliorating hypercapnia-induced immunosuppression improving resistance infection hypercapnia.