BIOCHEMICAL AND IMMUNOHISTOCHEMICAL CHARACTERIZATION OF HUMAN TYPE-XIX DEFINES A NOVEL CLASS OF BASEMENT-MEMBRANE ZONE COLLAGENS

Nineteen types, the product of 33 genes, comprise the collagen family of proteins. Types I, II, III, V, and XI constitute the fibrillar coll agens,whereas types IV, VI to X, and XII to XIX represent the structur ally diverse, nonfibrillar members. Type XIX collagen was discovered f rom the sequence of rhabdomyosarcoma cDNA clones, The type XIX chain c onsists of 1142 amino acids that contribute primarily to a unique five subdomain triple-helical region, To characterize the protein, to dete rmine the tissue distribution, and to provide some insight into its fu nction, we generated two type XIX-specific polyclonal antibodies, One was directed against a recombinant molecule containing amino-terminal sequences, and the second was derived from a synthetic peptide corresp onding to most of the short carboxy terminus, These antibodies were us ed in immunoblot assays of rhabdomyosarcoma cell/matrix homogenates to identify a 165-kd disulfide-bonded and bacterial collagenase-sensitiv e protein, Immunohistochemical analysis of type XIX collagen was perfo rmed for human skeletal muscle, spleen, prostate, kidney, liver, place nta, colon, and skin, In contrast to Northern blot hybridizations, whi ch showed very low levels of the 12-kb transcript in few tissues, the protein was found in all tissues examined, The type XIX collagen distr ibution was restricted to vascular, neuronal, mesenchymal, and some ep ithelial basement membrane zones, which is similar to the profile rece ntly established (Ref. 8) and further extended here for type XV collag en, Nevertheless, localization of type XIX exhibited significant diffe rences from type XV collagen that were particularly evident in the kid ney, liver, and spleen, This report, in conjunction with the type XV r esults and other studies of type XVIII collagen, indicates the existen ce of a new collagen subgroup founded on their widespread presence in basement membrane zones regardless of chain homology, In addition to t heir role in basement membrane-stromal interactions, the pronounced va scular association suggests involvement of these related collagen type s with angiogenic and pathological processes.