title: Alveolar macrophage activation by myeloperoxidase: a model for exacerbation of lung inflammation.
abstract: 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.
authors.affiliation: Department of Medical Microbiology and Immunology, University of South Florida, College of Medicine, Tampa 33612-4799, USA. kgratten@hsc.usf.edu
authors.forename: Ken
authors.initials: K
authors.lastname: Grattendick
authors.forename: Rodney
authors.initials: R
authors.lastname: Stuart
authors.forename: Erin
authors.initials: E
authors.lastname: Roberts
authors.forename: John
authors.initials: J
authors.lastname: Lincoln
authors.forename: Stanley S
authors.initials: SS
authors.lastname: Lefkowitz
authors.forename: Alex
authors.initials: A
authors.lastname: Bollen
authors.forename: Nicole
authors.initials: N
authors.lastname: Moguilevsky
authors.forename: Herman
authors.initials: H
authors.lastname: Friedman
authors.forename: Doris L
authors.initials: DL
authors.lastname: Lefkowitz
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology*; D051379:Mice; D009195:Peroxidase / Q000378:metabolism*; D010587:Phagocytosis; D011014:Pneumonia / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D016207:Cytokines; D009195:Peroxidase