Mechanism of impaired local hyaluronan turnover in bleomycin-induced lung injury in rat.
Hyaluronan, a linear polysaccharide, is accumulated in lung interstitium during different pathological conditions, causing interstitial edema and thereby impaired lung function. We investigated the mechanism of local hyaluronan turnover during the early phase of bleomycin-induced fibrotic lung injury in rats. The binding of [3H]hyaluronan to alveolar macrophages (AM) established from bleomycin-treated rats 1 and 5 days after induction of injury was decreased 8- and 15-fold, respectively, compared with that of AM from saline-treated control counterparts, but at day 14 returned almost to the normal level. Data was confirmed by quantitative cytochemistry, using fluorescein-labeled hyaluronan. Analysis of the expression of CD44, a receptor for hyaluronan, by Western blotting revealed a 30% increase of CD44 molecules expressed on AM from bleomycin-treated rats at day 5 compared with control rats. In particular a lower molecular mass form of CD44 appeared. No expression of the receptor for hyaluronan-mediated motility (RHAMM) could be detected. The internalization and degradation of [3H]hyaluronan by AM, obtained from bleomycin-treated rats at days 1, 5, and 14, were decreased about 65%, 35%, and 30%, respectively, compared with AM from the control rats. The AM lysosomal hyaluronidase activity did not differ significantly between bleomycin-treated and control rats. Our results indicate that a decreased hyaluronan binding capacity of AM may account for the impairment of internalization and thereby degradation of excessive hyaluronan during the early phase of fibrotic lung injury.
Teder
P
P
Department of Medical and Physiological Chemistry, Biomedical Center, Uppsala University, Sweden.
Heldin
P
P
D000818:Animals; D000964:Antimetabolites, Antineoplastic; D001665:Binding Sites / Q000502:physiology; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D004705:Endocytosis / Q000502:physiology; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D005374:Filtration; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism*; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000964:Antimetabolites, Antineoplastic; D001761:Bleomycin; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase