Sex dimorphism and inflammatory regulation of T-kininogen and T-kininogenase.
Studies were carried out in order to better understand hormonal and inflammatory regulation of the T-kininogen and T-kininogenase system. T-kininogen from rat serum and T-kininogenase from rat submandibular gland were purified to homogeneity, and specific antisera to the purified proteins were generated. Simple, sensitive and specific radioimmunoassays were developed for measuring both T-kininogen and T-kininogenase. The assays incorporated a modified poly(ethylene glycol) technique for separating free from antibody-bound forms. Optimal combinations of poly(ethylene glycol) and gamma-globulin were found, yielding low background and high specific binding. The assays can detect a minimum of 160 pg of T-kininogen and 80 pg of T-kininogenase per tube. Serial dilutions of sera from normal and turpentine-treated rats showed complete parallelism with the T-kininogen standard curve. T-kininogen levels in rat serum and rat tissues increased more than 10-fold following turpentine treatment, while T-kininogenase levels in the submandibular gland and other tissues remained unchanged. Through use of a kinin-directed kininogen monoclonal antibody, Western blots of two-dimensional gels of serum following acute inflammation showed increased levels of several kininogens which vary in both molecular weight and isoelectric point. Analysis of serum kininogen levels shows sexual dimorphism, with female rats having 3.9-fold higher levels than males. Contrarily, T-kininogenase levels in the submandibular gland of male rats are 2.4-fold higher than those in females. The studies also showed that the T-kininogen and T-kininogenase system is regulated by sex hormones. T-kininogen is an acute-phase protein whose rapid increase and mobilization following inflammation may provide a primary defense against proteolytic damage during trauma.
Chao
S
S
Department of Pharmacology, Medical University of South Carolina, Charleston 29425.
Chao
L
L
Chao
J
J
D000818:Animals; D015153:Blotting, Western; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D007610:Kallikreins / Q000302:isolation & purification / Q000378:metabolism*; D007704:Kininogens / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D014425:Turpentine
D007704:Kininogens; D007610:Kallikreins; D014425:Turpentine