Am. J. Respir. Cell Mol. Biol., Volume 18, Number 4, April, 1998 497-510

Mast Cell Collagenase Correlates with Regression of Pulmonary Vascular Remodeling in the Rat

Carol A. Tozzi, Smita Thakker-Varia, Shiu Y. Yu, Rena F. Bannett, Bonnie W. Peng, George J. Poiani, Frank J. Wilson, and David J. Riley

Departments of Medicine and Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey- Robert Wood Johnson Medical School, Piscataway, New Jersey; Department of Veterans Affairs New Jersey Healthcare System, Lyons, New Jersey; and Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, New York

Pulmonary vascular remodeling, produced by cell hypertrophy and extracellular matrix protein synthesis in response to hemodynamic stress, regresses after reduction of blood pressure, possibly by proteolysis of structural proteins. To test this postulate, we assessed the breakdown of extracellular matrix proteins and expression of collagenase and elastase in pulmonary arteries of rats exposed to hypoxia (10% O₂ for 10 d) followed by normoxia. During hypoxia, contents of collagen and elastin increased in pulmonary arteries and latent rat interstitial collagenase was expressed without increased collagenolytic activity or mRNA levels. At 3 days after normoxia, collagen and elastin contents decreased coincident with the new appearance of activated collagenase and transient increases in collagenolytic and elastolytic activities. The amount of immunoreactive collagenase, localized predominately in connective tissue-type mast cells, was increased in the adventitia and media of hypertensive vessels. We conclude that mast cells containing latent collagenase are recruited into the outer walls of pulmonary arteries during remodeling. It is possible that mast cell-derived collagenase contributes to collagen breakdown in pulmonary arteries during early recovery from hypoxia and plays a role in restoration of vascular architecture.

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