Malotilate Prevents Accumulation of Type III pN-Collagen, Type IV Collagen, and Laminin in Carbon Tetrachloride-induced Pulmonary Fibrosis in Rats

Abstract

Orally administered malotilate was studied as a protective antifibrotic agent with respect to experimentally induced pulmonary fibrosis in rats using immunohistochemical methods. Specific antibodies raised in rabbits against the aminoterminal propeptide of human type III procollagen and against two basement membrane proteins, the 7S domain of human type IV collagen and the P1 fragment of human laminin, were used for the immunohistochemical analysis, and the result was confirmed by morphometry. Intraperitoneally injected carbon tetrachloride significantly increased the volume densities of reticulin fibers, type III pN-collagen, type IV collagen, and laminin, whereas treatment with malotilate completely normalized these. Binding of the antibodies to rat antigens was also demonstrated by immunoelectron microscopy in which the collagen fibers with a typical periodic pattern were labeled positively with rabbit antitype III procollagen, whereas the amorphous basement membrane material reacted positively with rabbit antitype IV collagen and antilaminin, indicating good, specific cross-reactivity between these antibodies and the rat antigens. It is concluded that malotilate prevents the accumulation of type III pN-collagen and two basement membrane proteins, type IV collagen and laminin, in experimental pulmonary fibrosis, and can potentially be developed to provide a useful drug for preventing pulmonary fibrosis in humans.