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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At 5, 15, and 45 days following induction of interstitial pulmonary fibrosis by intratracheal administration of bleomycin in hamsters, glycosaminoglycan synthesis was measured, using [35S]sulfate. Total labeled sulfate incorporation into lung glycosaminoglycans was maximally increased over that of saline-instilled controls at 5 days (P less than or equal to 0.05), declined markedly at 15 days, and returned to control values at 45 days. Separation of the various labeled glycosaminoglycans by chondroitinase digestion and chromatography revealed a transient rise from controls (P less than or equal to 0.05) in the proportion of labeled chondroitin 4-sulfate at 5 days, followed by an increase from controls (P less than or equal to 0.05) in proportionate labeling of dermatan sulfate at 15 and 45 days postbleomycin. Autoradiography, using [35S]sulfate, performed at 21 days postbleomycin, revealed an increase from controls in film grain formation in areas of interstitial reaction. Grain formation was greatly reduced by pretreatment of the slide sections with hyaluronidase and chondroitinase, demonstrating the specificity of the label for glycosaminoglycans. The results indicate that glycosaminoglycan synthesis is significantly altered from normal in this model of interstitial lung disease and that dermatan sulfate is preferentially synthesized during the fibrotic phase of the lung reaction.
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PMID:Glycosaminoglycan synthesis in bleomycin-induced pulmonary fibrosis: biochemistry and autoradiography. 619 65

Pulmonary fibrosis is characterized by an accumulation of inflammatory cells in the lung interstitium, followed by an increased deposition of extracellular matrix. Macrophages play a vital role in this disease by mediating the progression from inflammation to fibrosis, but the mechanisms by which macrophages are retained at these sites are not fully understood. Although the transmigration of leukocytes is regulated by chemokines, glycosaminoglycans modulate the function of chemokines and the migration of leukocytes. Accordingly, we investigated the role of chondroitin sulfate proteoglycans (CSPGs) in a murine bleomycin-induced pulmonary fibrosis models. After intratracheal injection of bleomycin or saline, mice were randomized to receive one intravenous injection and continuous infusion of the CSPG-digesting enzyme chondroitinase ABC (ChABC), or vehicle, for 7 days. CSPGs were readily induced and progressively augmented after the bleomycin challenge. Although CSPGs inhibited the early CCL2-dependent recruitment of macrophages, deposited CSPGs retained macrophages in fibrotic interstitium in a CD44-dependent manner. Treatment with ChABC in vivo dramatically increased survival of the mice and reduced collagen deposition by inhibiting persistent macrophage accumulation. These results indicate a pivotal role for CSPGs in macrophage-mediated lung fibrogenesis and suggest a possible new therapeutic role for ChABC in pulmonary fibrosis.
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PMID:Treatment with chondroitinase ABC alleviates bleomycin-induced pulmonary fibrosis. 1787 45