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Am. J. Respir. Cell Mol. Biol., Volume 23, Number 4, October, 2000 475-484

A Role for Hyaluronan in Macrophage Accumulation and Collagen Deposition after Bleomycin-Induced Lung Injury

Rashmin C. Savani, Guangpei Hou, Ping Liu, Chao Wang, Elinor Simons, Paul C. Grimm,* Robert Stern, Arnold H. Greenberg, Horace M. DeLisser, and Nasreen Khalil

Division of Neonatology, Department of Pediatrics; Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Departments of Pediatrics and Medicine, and Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Manitoba, Canada; and Department of Pathology, University of California at San Francisco, San Francisco, California

Elevated concentrations of hyaluronan (HA) are associated with the accumulation of macrophages in the lung after injury. We have investigated the role of HA in the inflammatory and fibrotic responses to lung injury using the intratracheal instillation of bleomycin in rats as a model. After bleomycin-induced lung injury, both HA content in bronchoalveolar lavage (BAL) and staining for HA in macrophages accumulating in injured areas of the lung were maximal at 4 d. Increased HA in BAL correlated with increased locomotion of isolated alveolar macrophages. HA-binding peptide was able to specifically block macrophage motility in vitro. Importantly, systemic administration of HA-binding peptide to rats before injury not only decreased alveolar macrophage motility and accumulation in the lung, but also reduced lung collagen alpha  (I) messenger RNA and hydroxyproline contents. We propose a model in which HA plays a critical role in the inflammatory response and fibrotic consequences of acute lung injury.

*  Current address: Division of Nephrology, Department of Pediatrics, University of California San Diego, La Jolla, CA.




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