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Alveolar macrophage activation by myeloperoxidase: a model for exacerbation of lung inflammation
Ken Grattendick1, Rodney Stuart, Erin Roberts
1Department of Medical Microbiology and Immunology, University of South Florida, College of Medicine, Tampa 33612-4799, USA. kgratten@hsc.usf.edu
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.
Insights
Neutrophil myeloperoxidase (MPO) and its inactive form (iMPO) activate lung macrophages, increasing inflammation. This interaction contributes to the overall inflammatory state in the lungs.
Area of Science:
- Pulmonary immunology
- Cellular inflammation
- Innate immune response
Background:
- Lung inflammation involves leukocyte infiltration, particularly neutrophils.
- Tumor necrosis factor-alpha is implicated in inflammatory processes.
- Alveolar macrophages (AMø) play a role in lung immunity.
Purpose of the Study:
- To investigate the interaction between neutrophil-derived myeloperoxidase (MPO) and alveolar macrophages (AMø).
- To determine the effect of enzymatically active MPO and inactive MPO (iMPO) on AMø function.
Main Methods:
- Rat AMø were exposed to recombinant MPO and iMPO.
- Respiratory burst (RB) activity was measured.
- Macrophage-mediated intracellular candidacidal activity was assessed.
- Cytokine gene and product expression was analyzed.
Main Results:
- Both MPO and iMPO increased AMø respiratory burst (RB).
- iMPO induced a greater RB enhancement than MPO.
- Intracellular candidacidal activity was similar for MPO and iMPO.
- iMPO showed greater upregulation of cytokine genes and products.
Conclusions:
- Neutrophil-derived MPO and iMPO stimulate AMø at inflammatory sites.
- This stimulation leads to an increased inflammatory and cytotoxic state in macrophages.
- The interaction contributes to the overall lung inflammatory response.