Study on mechanisms of metalloproteinase release from human eosinophils

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Recently it has been suggested that proteinase from various cells may be involved in cell invasion, tissue damage and tissue remodelling in inflammatory diseases and malignant diseases. Also in bronchial asthma, there is a possibility that proteinase from leukocytes, especially matrix metalloproteinase-9 (MMP-9), induces disruption of extracellular matrix and basement membranes leading to airway remodelling. However, it is unclear by what stimulus or how MMP-9 is released from leukocytes including eosinophils in tissue.In 1999, we mainly examined MMP-9 release from human neutrophils in response to various stimuli. The results were as follows. Among three fractions of mononuclear cells, neutrophils and eosinophils from human leukocytes, neutrophils released the largest amount of MMP-9. Among C5a, FMLP and PAF as stumuli for neutrophils, FMLP induced the release of the largest amount of MMP-9. The stimulus effect of FMLP was maximal at 10^<-8>M.Preincubation with GM-CSF enhanced FMLP-induced MMP-9 release.In 2000, we examined MMP-9 release from human eosinophils under various conditions, and also examined signal transduction in MMP-9 release from human neutrophils. The results were as follows. Human eosinophils did not release significant amount of MMP-9 in response to C5a, FMLP or PAF either without or with IL-5 priming. Next, pertussis toxin (PTX) pretreatment clearly inhibited FMLP-induced MMP-9 release from human neutrophils. Therefore, it was suggested that PTX-sensitive G protein may be involved in signal transduction in FMLP-induced MMP-9 release. In summary, it was indicated that MMP-9 is mostly released from neutrophils among human leukocytes and that FMLP most effectively induces MMP-9 release, in which PTX-sensitive G protein may be involved in signal transduction.