Matrix metalloproteinase-9 release from human leukocytes.
Although proteinases are thought to contribute to the pathogenesis of bronchial asthma and COPD, the mechanism of proteinase release from inflammatory cells has not been thoroughly clarified. We examined matrix metalloproteinase (MMP-9) release from human leukocytes using soluble agonists such as C5a, FMLP, and PAF. Mononuclear cells, neutrophils, and eosinophils isolated from human leukocytes were incubated with C5a, FMLP, or PAF for 20 min. MMP-9 in supernatants was measured by ELISA. Among mononuclear cells, neutrophils, and eosinophils, MMP-9 was released mainly from neutrophils. FMLP was the most effective stimulus of MMP-9 release from neutrophils among three agonists: C5a, FMLP, and PAF. GM-CSF clearly enhanced FMLP-induced MMP-9 release. Pretreatment of neutrophils with pertussis toxin (PTX) resulted in the inhibition of FMLP-induced MMP-9 release, indicating the contribution of PTX-sensitive G-proteins to intracellular signal transduction in FMLP-induced MMP-9 release. These results suggest that neutrophils release large amounts of MMP-9 in response to FMLP, which is a bacterial product analogue. It cannot be excluded that MMP-9 released from neutrophils may be involved in the pathogenesis of bronchial asthma and COPD.
Takafuji
Shigeru
S
Department 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
Ishida
Akira
A
Miyakuni
Yuji
Y
Nakagawa
Takemasa
T
D001249:Asthma / Q000276:immunology; D015936:Complement C5a / Q000494:pharmacology*; D003571:Cytochalasin B / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D037342:Pertussis Toxin; D010972:Platelet Activating Factor / Q000494:pharmacology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology
D010972:Platelet Activating Factor; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D037342:Pertussis Toxin; D020780:Matrix Metalloproteinase 9