Collagen polymorphism in idiopathic chronic pulmonary fibrosis

Abstract

Collagens in normal human lung and in idiopathic chronic fibrosis were investigated in terms of their covalent structure and compared for possible alterations in the diseased state. Collagens were solubilized by limited digestion with pepsin under nondenaturing conditions, and after purification they were fractionated into types I and III. Carboxymethylcellulose and agarose chromatography of both types I and III collagens, and amino acid and carbohydrate analyses of the resulting α chains indicated that the α1 (I), α2, and α1 (III) chains of normal human lung were identical with the human skin α chains in all respects examined except that the normal lung chains contained higher levels of hydroxylysine. Examination of collagens obtained from the diseased lung revealed that the content of hydroxylysine of the α1 (I) and the α1 (III) chains appeared to be diminished as compared to the normal lung chains. The values, expressed as residues per 1,000 residues, are 7.1 and 8.3 for the α1 (I) and the α1 (III) chains, respectively, as compared to 10.0 and 11.1 for the α chains from the normal tissue. The chromatographic properties and amino acid and carbohydrate composition of the α chains from the diseased tissue were otherwise indistinguishable from those of normal lung. In addition, isolation and characterization of the CNBr peptides of α1 (I), α2 and α1 (III) from the diseased lung revealed no significant differences from the CNBr peptides from other human tissues reported previously. Normal and diseased lungs were also digested with CNBr, and the resultant α1 (I) and α1 (III) peptides were separated chromatographically. The relative quantities of these peptides indicate that type III collagen constitutes 33% of the total collagen in normal human lung, with the remainder being type I, whereas in idiopathic chronic pulmonary fibrosis, the relative content of type III collagen is markedly diminished, ranging from 12 to 24% in different patients. These results indicate that an alteration in tissue collagen polymorphism as well as subtle variations in the collagen structure accompany the fibrotic process in the diseased state, and suggest that these alterations may have possible pathogenetic implications.