Role of Interferon in the Cellular Response of the CNS Macrophage, the Microglia,During Injury and Inflammation

摘要

Our lab has studied the response of the CNS macrophage, the microglia to injuryand inflammation. Using an in vitro approach, we have shown that microglia cultured from the cerebral cortices of neonatal animals (rat, mouse, hamster or human) have the same functional responses as non-CNS macrophages. That is, they demonstrate chemotaxis, express macrophage-like surface antigens and they produce a variety of cytoactive factors including proteases, interleukin-1 and reactive oxygen species (superoxide anion and nitric oxide). We found that both inflammatory and immune mediators (lipopolysaccharide and interferons, respectively) enhance the production of superoxide anion but do not directly activate the NADPH oxidase. These agents also increase nitric oxide (NO) production but in a very different time frame than that found for superoxide anion. Treatment of microglia with isopreterenol or dexamethazone depressed the microglial production of ROS. Our studies also demonstrated that human and hamster microglia do not produce NO in response to the same stimulating factors used in rat or mouse microglia. Hamster and human microglia did not produce NO except when treated with the double stranded polyribonucleotide, poly inosinic acid: poly cytidylic acid (Poly I:C). These findings have important consequences to the understanding of the response of humans to inflammation or injury.