Proteinase inhibitor 6: a multifunctional intracellular serpin

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We have discovered and characterized an unusual protease inhibitor that is widely distributed in the body. We have shown that the inhibitor is present in immune cells that are responsible for fighting bacterial infection, and that its role is probably to protect these cells against a powerful endogenous protease produced to destroy ingested bacteria. The inhibitor probably has additonal roles because it is present in developing and adult brain, skin and other blood cells. In these tissues we have evidence that inhibitor regulates other, unidentified, proteases. The purpose of this grant is to identify these proteases, and to elucidate the physiological significance of the inhibitor by studying mice that lack it.