Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
Characterization of latent transforming growth factor-beta from human seminal plasma.
Am J Reprod Immunol. 1995 Apr;33(4):282-91. Unique Identifier : AIDSLINE MED/96037778 Nocera M; Chu TM; Department of Diagnostic Immunology Research and Biochemistry,; Roswell Park Cancer Institute, New York State Department of; Health, Buffalo 14263, USA.
Abstract:
PROBLEM: Human seminal plasma is known to exhibit immunosuppressive activity. Transforming growth factor beta (TGF-beta) has been identified as an immunosuppressive factor in human seminal plasma. Biologically active TGF-beta represents a family of 25-kDa homodimeric proteins linked with disulfide bonds. TGF-beta associates with high molecular weight proteins noncovalently to form a type of latency that is biologically inactive. Quantitative distribution of active form of TGF-beta versus inactive latent form of of TGF-beta, and mechanism of the TGF-beta activation in human seminal plasma remain to be elucidated. PURPOSE: To characterize seminal plasma latent form of TGF-beta, including its concentration, and the mechanism underlying the activation of TGF-beta. METHOD: Gel filtrations on ACA-34 and Biogel P-60 were used to fractionate seminal plasma. TGF-beta was measured by enzyme immunoassay using antibodies specific for TGF-beta 1 and TGF-beta 2, respectively. Radioreceptor assay with recombinant human [125I]-TGF-beta 1 was applied to qualitatively identify TGF-beta 1. Kinetic experiments with various pH, temperature and time, along with protease inhibitors, were performed to delineate the activation mechanism of latent TGF-beta 1. RESULTS: Human seminal plasma contained both TGF-beta 1 and TGF-beta 2, predominantly in latent form. The total concentration of TGF-beta 1 averaged 238 ng/ml versus an average of 18 ng/ml for TGF-beta 2. The in vitro activation or release of TGF-beta 1 from latent TGF-beta 1 was achieved only at acidic pH of < 4.0, and was time and temperature dependent. At pH 3.7 and 37 degrees C, a significant activation of latent TGF-beta 1 was achieved after an incubation of only 15 min, reached the maximum at 120 min, and the activated TGF-beta 1 remained relatively stable for at least 24 h. The activation was not inhibitable by a series of protease inhibitors examined, alone or in combination (e.g., phenyl-methylsulfonyl fluoride, E-64, pepstatin, leupeptin, ethylenediamine tetraacetic acid). Competitive radioreceptor assay established the functional identity of TGF-beta 1 in human seminal plasma with recombinant human TGF-beta 1. CONCLUSION: Human seminal plasma TGF-beta is biologically activated from high molecular weight latent TGF-beta by acid pH. The acidic environment of female lower genital tract could represent an in vivo physiological condition for activation of seminal plasma TGF-beta that may immunologically protect the integrity of sperm.
Keywords: Animal Chromatography Female Genitalia, Female/METABOLISM Human Hydrogen-Ion Concentration HIV Infections/TRANSMISSION Immunoenzyme Techniques Male Mink Reference Standards Semen/*CHEMISTRY/IMMUNOLOGY/PHYSIOLOGY Transforming Growth Factor beta/*ANALYSIS/IMMUNOLOGY/ *PHARMACOKINETICS JOURNAL ARTICLE
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Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
