Expression of neutrophil metalloproteinase-9 (gelatinase) under inflammatory conditions

Abstract

Matrix metalloproteinase (MMP) -9 plays an important role in neutrophil extravasation and migration by its ability to degrade the major components of basement membrane. To evaluate the expression of neutrophil MMP-9 (gelatinase) under inflammatory conditions, we examined the levels of MMP-9 and its mRNA in neutrophils from glycogen-induced peritoneal inflammation of guinea pigs. MMP-9 level in peritoneal neutrophils was essentially the same as that in blood neutrophils, although peritoneal neutrophils were assumed to have extracellularly released MMP-9 from the granules during infiltration into the peritoneal cavity. Interestingly, MMP-9 mRNA was expressed more abundantly in peritoneal neutrophils than in blood neutrophils. Moreover, actinomycin D-or cycloheximide-treatment significantly suppressed the MMP-9 levels in blood and peritoneal neutrophils. In addition, when blood neutrophils from non-injected animals were stimulated with 10-7 M N-formyl-Met Leu-Phe, 10μg/ml lipopolysaccharide, 10 ng/ml phorbol 12-myristate 13-acetate, 10-8 MIL-8 or 100 U/ml tumor necrosis factor-α, expression of MMP-9 mRNA was markedly increased. The present observations indicate that MMP-9 gene is transcribed, and MMP-9 protein is synthesized in neutrophils during inflammation. Moreover, the transcription of MMP-9 gene can be upregulated in neutrophils by stimulation with inflammatory mediators, even after neutrophils have been matured.