Enzymatic basis for bioenergetic differences of alveolar versus peritoneal macrophages and enzyme regulation by molecular O2.

Abstract

A B S T R A C T Alveolar macrophages (AM) and peritoneal macrophages (PM) originate from common precursor cells, but function in different 02 environments. In the present studies, the impact of different 02 tensions on cell metabolism has been quantitatively determined, an enzymatic basis for these differences established, and a mechanism which regulates enzymatic differences demonstrated. 02 consumption and lactate production were compared in rabbit AM and PM in air and nitrogen. In air, AM demonstrate significantly greater 02 utilization. In nitrogen, (where glycolysis is the major source of energy provision) lactate production is two-to threefold greater in the PM.A comparison of several enzymes of energy metabolism in AM and PM indicate that one basis for the differences in cell energetics is a difference in activity of key enzymes of both the oxidative phosphorlylative and the glycolytic sequences.Exposure of cultivated AM to hypoxic conditions results in changes in the activity of these enzymes such that the AM closely resembles the PM. A key enzyme in oxidative phosphorylation (cytochrome oxidase) shows decreased activity and reaches values similar to those found in the PMI. A key enzyme in glycolysis (pyruvate kinase) shows increased activity to values resembling those found in the PM. These alterations in enzyme pattern occur in isolated cell systems, suggesting that molecular 02 modifies the Dr.

Inflammatory Cytokines and Hypoxia Contribute to 18F-FDG Uptake by Cells Involved in Pannus Formation in Rheumatoid Arthritis

“…Hypoxia changes the energy supply of cells into anaerobic glycolysis. According to studies of glucose use by macrophages, differences in O 2 tension lead to alterations in the rate of oxidative phosphorylation and glycolysis, and hypoxia upregulates glucose uptake and lactate production (24,25). Furthermore, it is known that macrophages regulate many factors associated not only with survival, such as the glucose transporter and vascular endothelial growth factor, but also inflammation, such as TNFa and IL-1, under hypoxic conditions (26).…”

Reactive species mechanisms of cellular hypoxia-reoxygenation injury

“…Hypoxia decreases apparent expression of cytochrome oxidase in AM, a change in the electron transport system that would predispose to O 2 Ϫ formation (101). The antioxidant enzymes SOD, glutathione peroxidase (GP), and catalase are all two-to threefold higher in aerobic AM than in hypoxic PM (113), apparently reflecting the different levels of oxygenation. Similar changes in antioxidant enzyme phenotype occur when normally aerobic cells are cultured in hypoxia (48,59,101).…”

“…A number of mitochondrial enzymes, including cytochrome oxidase and manganese superoxide dismutase (Mn SOD), decrease in activity in hypoxia (81,101,113), with predicted effects on oxygen metabolism. Cellular hypoxia inhibits expression of the multisubunit cytochrome oxidase (complex IV), the final intramitochondrial site of oxidative phosphorylation.…”

“…Cellular hypoxia inhibits expression of the multisubunit cytochrome oxidase (complex IV), the final intramitochondrial site of oxidative phosphorylation. Cytochrome oxidase activity of aerobic mouse lung macrophages decreases ϳ40% when incubated anaerobically for 96 h (113). Loss of cytochrome oxidase activity leads to cellular injury during reoxygenation, because absence of the final electron acceptor increases ROS production by more proximal complexes (33).…”

Response of a phagocyte cell system to products of macrophage breakdown as a probable mechanism of alveolar phagocytosis adaptation to deposition of particles of different cytotoxicity.

“…Thus, we have grounds to consider the observed increase in oxygen consumption under the stimulating action of PMB in 1 x 107 concentration on the average of 31.8% for PM (from 2.22 + 0.07 to 2.92 + 0.17 nA 02/min per 106 cells, p < 0.001) and of 21.6% for AM (from 3.66 + 0.2 to 4.42 + 0.24, p < 0.02) to be a result of a real enhancement of macrophage metabolism. When the number of cells in a polarograph unit was equal, the PMB stimulating effect was equal for AM and PM, in spite of the known peculiarities of aerobic metabolism of AM (52,(63)(64)(65)(66).…”