Particulate matter induction of pulmonary gelatinase A, gelatinase B, and tissue inhibitor of metalloproteinase expression

Celatinase A and gelatinase B are matrix metalloproteinases (MMPs) that are capable of degrading type IV collagen as well as other major components of basement membranes. These MMPs are also involved in modulating inflammatio n and tissue remodeling. Previous studies have shown the induction of pulmo nary matrilysin, another MMP, following exposure to either combustion or am bient particulate matter (PM). In the present study, we examined whether ge latinase A, gelatinase B, or tissue inhibitor of metalloproteinase (TIMP) w as affected following exposure to PM. Sprague-Dawley rats were exposed to a combustion PM (residual oil fly ash, ROFA, 2.5 mg/rat) or saline by intrat racheal instillation and examined at 6 to 72 h postexposure. Changes in gel atinase A, gelatinase B, and TIMP-1 and -2 mRNA levels were determined usin g reverse transcription (RT) polymerase chain reaction (PCR). ROFA exposure increased the mRNA levels of gelatinase A and TIMP-1. However, gelatinase B mRNA, not expressed in control animals, was significantly induced from 6 to 24 h following ROFA exposure. Western blot analysis confirmed the presen ce of gelatinase A and B protein in lung tissue following ROFA exposure. Im munocytochemical analysis revealed that alveolar epithelial cells and infla mmatory cells were major cellular sources for the pulmonary gelatinase A an d B expression. To compare the effects of ambient PM with that of combustio n PM and to further examine effects of ambient PM size on MMP induction, an imals were treated with the same dose of the size-fractionated ambient PM [ PM<1.7, PM1.7-3.7, PM3.7-20 (size indicated in micrometers) collected from Washington, DC]. Gelatinase A, gelatinase B, and TIMP gene expression and c ellular distributions were assessed using RT-PCR and immunocytochemistry, r espectively. interestingly, gelatinase B was significantly induced to the s ame extent by all three size-fractionated ambient PM. Gelatinase A and TIMP -1 expression were not changed, while TIMP-2 expression was slightly decrea sed by PM<1.7 and PM1.7-3.7. Immunocytochemically, gelatinase A, gelatinase B, and TIMP-2 expression were localized mainly to the terminal bronchiole region and associated with inflammatory cells in ambient PM exposed animals . Thus, we have provided further evidence that MMP and TIMP expression are altered following exposure to either combustion or ambient PM supporting th e hypothesis that MMP may be involved in pathogenesis of PM-induced lung in jury.