title: Circulating autoantibodies to mammalian tissue kallikreins.
abstract: Autoantibodies to tissue kallikrein (EC 3.4.21.35) were discovered in normal human, rat, mouse, and guinea pig sera. Three independent methods--binding of iodolabeled antigen, enzyme-linked immunosorbent assay (ELISA), and immunoblotting--were used to demonstrate these kallikrein autoantibodies. Autoantibodies from rat and human sera were purified, using rat and human tissue kallikrein-affinity chromatography, respectively. Purified rat kallikrein autoantibody bound 50% of 125I-labeled rat urinary kallikrein upon incubation of antibody at 2.5 X 10(-10) M. The subtypes of rat and human kallikrein autoantibodies were determined by an ELISA, using antisera to immunoglobulin subclasses. In both species, autoantibody was predominantly IgG (approximately 80%) and some IgM (approximately 20%). Purified autoantibodies from rat and human sera were separated on sodium deodecyl sulfate-polyacrylamide gels, and their subunits were identified by Western blot analyses, using anti-rat and anti-human IgG antibodies, respectively. When primary cultures of mouse spleen cells were incubated for 1 to 5 days with lipopolysaccharide (1 to 5 micrograms/ml), the anti-kallikrein antibodies in the media increased up to seven-fold. We have demonstrated circulating autoantibodies that recognize and bind both autologous and heterologous kallikrein; however, their significance to the function of the tissue kallikrein-kinin system in normal and disease states remains to be explored.
authors.affiliation: Department of Pharmacology, Medical University of South Carolina, Charleston 29425.
authors.forename: J
authors.initials: J
authors.lastname: Chao
authors.forename: R K
authors.initials: RK
authors.lastname: Mayfield
authors.forename: L
authors.initials: L
authors.lastname: Chao
mesh_terms: D000818:Animals; D000917:Antibody Formation; D037263:Asialoglycoprotein Receptor; D001323:Autoantibodies / Q000032:analysis* / Q000145:classification; D001666:Binding Sites, Antibody; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006168:Guinea Pigs; D006801:Humans; D007610:Kallikreins / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D011863:Radioimmunoassay; D051381:Rats; D011971:Receptors, Immunologic / Q000032:analysis; D013154:Spleen / Q000378:metabolism
chemical_list: D037263:Asialoglycoprotein Receptor; D001323:Autoantibodies; D008070:Lipopolysaccharides; D011971:Receptors, Immunologic; D007610:Kallikreins