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- 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- , TNF- .
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Copyright © 2002 American Thoracic Society.
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