Document 0807
 DOCN  M9610807
 TI    Characterization of latent transforming growth factor-beta from human
       seminal plasma.
 DT    9601
 AU    Nocera M; Chu TM; Department of Diagnostic Immunology Research and
       Biochemistry,; Roswell Park Cancer Institute, New York State Department
       of; Health, Buffalo 14263, USA.
 SO    Am J Reprod Immunol. 1995 Apr;33(4):282-91. Unique Identifier : AIDSLINE
       MED/96037778
 AB    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.
 DE    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

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).