Ga1 alpha(1,3) Ga1 epitope in porcine small intestinal submucosa

Small intestinal submucosa (SIS) is a naturally occurring, acellular biomat erial derived from porcine jejunum, which promotes constructive tissue remo deling when applied as a xenogeneic graft material. Galactosyl-alpha(1,3)ga lactose (Gal) is a cell-associated epitope responsible for hyperacute rejec tion of porcine whole-organ xenografts in primates. Because SIS is harveste d from porcine tissue, it may contain the Gal epitope. The goals of this st udy were to determine if Gal is present in SIS and, if it is present, to de termine if human serum complement can be activated in vitro following expos ure to porcine-derived SIS. SIS was probed for Gal by immunohistochemical m ethods and by lectin-peroxidase staining. SIS stained strongly positive wit h human serum, which contains naturally occurring antibodies to Gal, follow ed by anti-immunoglobulin G (IgG) or anti-IgM peroxidase conjugate. Blockin g with the lectin I-B-4, which is specific for the Gal epitope, decreased t he intensity of staining. Exposure of SIS to alpha-galactosidase reduced st aining to negligible amounts. The Gal epitope is distributed transmurally t hroughout the SIS material. Subtyping of the immunoglobulins that bind to S IS showed that IgG(2) is the major immunoglobulin of human plasma that bind s to SIS. SIS did not activate complement in vitro as measured by radioimmu noassay for C3a.