Seyer J M, Hutcheson E T, Kang A H
J Clin Invest. 1976 Jun;57(6):1498-507. doi: 10.1172/JCI108420.
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 alpha-chains indicated that the alpha 1 (I), alpha 2, and alpha 1 (III) chains of normal human lung were identical with the human skin alpha-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 alpha 1 (I) and the alpha 1 (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 alpha 1 (I) and the alpha 1 (III) chains, respectively, as compared to 10.0 and 11.1 for the alpha-chains from the normal tissue. The chromatographic properties and amino acid and carbohydrate composition of the alpha-chains from the diseased tissue were otherwise indistinguishable from those of normal lung. In addition, isolation and characterization of the CNBr peptides of alpha 1 (I), alpha 2 and alpha 1 (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 alpha 1 (I) and alpha 1 (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.
对正常人肺组织和特发性慢性纤维化肺组织中的胶原蛋白进行了共价结构研究，并比较了疾病状态下可能发生的变化。在非变性条件下用胃蛋白酶有限消化使胶原蛋白溶解，纯化后将其分为I型和III型。对I型和III型胶原蛋白进行羧甲基纤维素和琼脂糖层析，以及对所得α链进行氨基酸和碳水化合物分析，结果表明，正常人肺组织的α1（I）、α2和α1（III）链在所有检测方面均与人皮肤α链相同，只是正常肺组织的链中羟赖氨酸含量较高。对患病肺组织中获得的胶原蛋白进行检测发现，与正常肺组织的链相比，α1（I）和α1（III）链的羟赖氨酸含量似乎有所减少。以每1000个残基中的残基数表示，α1（I）和α1（III）链的值分别为7.1和8.3，而正常组织α链的值为10.0和11.1。患病组织α链的层析特性、氨基酸和碳水化合物组成在其他方面与正常肺组织的α链无法区分。此外，对患病肺组织中α1（I）、α2和α1（III）的溴化氰肽进行分离和表征，结果显示与先前报道的其他人体组织的溴化氰肽没有显著差异。正常和患病肺组织也用溴化氰消化，所得的α1（I）和α1（III）肽通过层析分离。这些肽的相对含量表明，III型胶原蛋白占正常人肺组织总胶原蛋白的33%，其余为I型，而在特发性慢性肺纤维化中，III型胶原蛋白的相对含量明显减少，不同患者中其含量在12%至24%之间。这些结果表明，在疾病状态下，纤维化过程伴随着组织胶原蛋白多态性的改变以及胶原蛋白结构的细微变化，提示这些改变可能具有潜在的致病意义。
