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Am. J. Respir. Cell Mol. Biol., Volume 26, Number 6, June, 2002 716-722

Alveolar Macrophage Activation by Myeloperoxidase
A Model for Exacerbation of Lung Inflammation

Ken Grattendick, Rodney Stuart, Erin Roberts, John Lincoln, Stanley S. Lefkowitz, Alex Bollen, Nicole Moguilevsky, Herman Friedman, and Doris L. Lefkowitz

Department of Medical Microbiology and Immunology, University of South Florida, College of Medicine, Tampa, Florida; Department of Biological Sciences, Texas Tech University, Lubbock, Texas; and Department of Applied Genetics, Université Libre de Bruxelles, Gosselies, Belgium

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 (AMø). Rat AMø exposed to either enzymatically active recombinant MPO or enzymatically inactive MPO (iMPO) exhibited an increased respiratory burst (RB). When iMPO was employed, the enhancement of the RB was greater than that observed with MPO. Although the RB was greater with iMPO, macrophage (Mø)-mediated intracellular candidic activity was equivalent for both MPO and iMPO. It is known that pro- inflammatory cytokines contribute to the inflammatory process. When rat AMø 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 AMø, resulting in an increased inflammatory and cytotoxic state, and thereby contributing to the general lung inflammatory response.


Abbreviations: alveolar macrophages, Amø; bovine serum album, BSA; Dulbecco's modified Eagle's medium, DMEM; dimethyl sulfoxide, DMSO; fetal bovine serum, FBS; glyceraldehyde-3-phosphate dehydrogenase, GAPDH; horseradish peroxidase, HRP; interleukin-8, IL-8; enzymatically inactive myeloperoxidase, iMPO; limulus amoebocyte lysate test, LAL; lipopolysaccharide, LPS; macrophage mannose receptor, MMR; enzymatically active recombinant myeloperoxidase, MPO; phosphate-buffered saline, PBS; polymorphonuclear leukocyte, PMN; respiratory burst, RB; relative light units, RLU; reactive oxygen intermediates, ROI; tetramethyl benzidine, TMB; tumor necrosis factor-alpha , TNF-alpha .




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