A Negative Role for Collagenase in Observed Differences between Human Normal and Rheumatoid Polymeric Collagens

Abstract

Studies on the action of mammalian collagenases have tended to use as substrate either tropocollagen monomers in solution or “native fibrils” assembled in vitro from such monomers. Both these forms of collagen contain only intramolecular cross-links, that is cross-links between chains within the same tropocollagen molecule, and no stable crosslinks between one tropocollagen molecule and another occur. The very lack of such intermolecular cross-links is, of course, the essential reason for their solubility. Rat tail tendon and guinea pig skin have also been used as substrates for mammalian collagenase, and in both instances the assumption has been made that the collagen fibers of these tissues were intermolecularly cross-linked and, therefore, insoluble. However, it has been shown that rat tail tendon collagen and guinea pig skin collagen can, with a little patience, be totally dissolved in dilute acetic acid (Hamerman and Schubert, 1968; Forest and Jackson, in press). It has also been observed that the denatured products of these solubilized collagen fibers contain no intermolecular crosslinked forms (Forest and Jackson). This would suggest that the forces holding together the fibers of rat tendon and guinea pig skin collagen are not stable covalent bonds but hydrophobic and hydrogen bonds. In the human situation, on the other hand, the collagen fibers visible in the intact tissue in the light microscope are quite insoluble in dilute acetic acid and are known to contain extensive inter-molecular cross-links.