Alveolar macrophage activation by myeloperoxidase - A model for exacerbation of lung inflammation

Inflammation of the lung is characterized by the influx of increased numbers of various leukocytes including polymorphonuclear leukocyte (PMN) neutrophils. In addition to cells, numerous studies have pointed to the role of tumor necrosis factor-alpha in the inflammatory process. This study addresses a previously unrecognized interaction between neutrophil-derived myeloperoxidase (MPO) and resident alveolar macrophages (AM empty set). Rat AM empty set exposed to either enzymatically active recombinant MPO or enzymatically inactive MPO (iMPO) exhibited an increased respiratory burst (1113). When iMPO was employed, the enhancement of the RB was greater than that observed with MPO. Although the RB was greater with iMPO, macrophage (M empty set)-mediated intracellular candidic activity was equivalent for both MPO and iMPO. It is known that proinflammatory cytokines contribute to the inflammatory process. When rat AM empty set were exposed to both forms of myeloperoxidase, iMPO demonstrated greater upregulation of cytokine genes as well as product. These data suggest that at the site of inflammation, neutrophil-derived MPO and iMPO stimulate AMo, resulting in an increased inflammatory and cytotoxic state, and thereby contributing to the general lung inflammatory response.