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Matrix metalloproteinase-9 release from human leukocytes.
Shigeru Takafuji1, Akira Ishida, Yuji Miyakuni
1Department of Internal Medicine, Toyoko Hospital, St. Marianna University School of Medicine, 3-435 Kosugi, Nakahara-ku, Kawasaki-City, Kanagawa 211-0063, Japan. takafuji@marianna-u.ac.jp
Summary
Neutrophils release matrix metalloproteinase-9 (MMP-9) in response to specific stimuli like FMLP. This release, enhanced by GM-CSF and mediated by G-proteins, may contribute to inflammatory lung diseases.
Area of Science:
- Immunology
- Respiratory Medicine
- Cell Biology
Background:
- Proteinases are implicated in the pathogenesis of bronchial asthma and COPD.
- The precise mechanisms of proteinase release from inflammatory cells remain unclear.
Purpose of the Study:
- To investigate the release of matrix metalloproteinase-9 (MMP-9) from human leukocytes.
- To identify the primary cell type responsible for MMP-9 release and the stimuli that trigger it.
Main Methods:
- Human leukocytes (mononuclear cells, neutrophils, eosinophils) were isolated.
- Cells were incubated with soluble agonists: C5a, FMLP, and PAF.
- MMP-9 levels in supernatants were quantified using ELISA.
- The role of GM-CSF and pertussis toxin (PTX)-sensitive G-proteins was assessed.
Main Results:
- Neutrophils were the primary source of MMP-9 release among tested leukocytes.
- FMLP was the most potent stimulus for MMP-9 release from neutrophils.
- Granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly enhanced FMLP-induced MMP-9 release.
- Pertussis toxin (PTX) inhibited FMLP-induced MMP-9 release, indicating G-protein involvement.
Conclusions:
- Neutrophils release substantial amounts of MMP-9, particularly in response to FMLP.
- The signaling pathway for FMLP-induced MMP-9 release involves PTX-sensitive G-proteins.
- Neutrophil-derived MMP-9 may play a role in the pathogenesis of bronchial asthma and COPD.