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

Abstract

Elevated concentrations of hyaluronan (HA) are associated with the accumulation of macrophages in the lung after in- jury. 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 la- vage (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 alveo- lar macrophages. HA-binding peptide was able to specifically block macrophage motility in vitro. Importantly, systemic ad- ministration of HA-binding peptide to rats before injury not only decreased alveolar macrophage motility and accumula- tion in the lung, but also reduced lung collagen a (I) messen- ger 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.