A role for hyaluronan in macrophage accumulation and collagen deposition after bleomycin-induced lung injury

Elevated concentrations of hyaluronan (HA) are associated with the accumula tion 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 s taining for HA in macrophages accumulating in injured areas of the lung wer e maximal at 4 d. Increased HA in BAL correlated with increased locomotion of isolated alveolar macrophages. HA-binding peptide was able to specifical ly block macrophage motility in vitro. Importantly, systemic administration of HA-binding peptide to rats before injury not only decreased alveolar ma crophage motility and accumulation in the lung, but also reduced lung colla gen alpha (I) messenger RNA and hydroxyproline contents. We propose a model in which HA plays a critical role in the inflammatory response and fibroti c consequences of acute lung injury.