Human seminal plasma contains multiple immunosuppressive factors that down-regulate innate immunity in the female reproductive tract. These immunosuppressive factors function to protect spermatozoa from the female immune system. However, the immunosuppressive effects potentially increase susceptibility of the female genital tract to infection by sexually transmitted diseases, including HIV. Preliminary studies from our laboratory identified galectin-3 on prostasomes, membranous vesicles in seminal plasma that inhibit leukocyte function. Significantly, galectin-3 receptors are expressed on leukocytes, galectin-3 exhibits immunomodulatory properties, and galectin-3 functions in pathogen-host cell interactions. Therefore, we hypothesize that galectin-3 contributes to the immunosuppressive properties of prostasomes and facilitates sexually transmitted infections. The overall goal of the current project is to investigate galectin-3 function in prostasomes with specific regard to immunosuppression.
The aims of the proposed project are to identify the specific galectin-3 binding ligands in prostasomes by microsequence analysis and to investigate the localization and function of galectin-3 in prostasomes. Surface localization of galectin-3 and its ligands on prostasomes will be investigated using immunoelectron microscopy and flow cytometry. The role of galectin-3 in prostasome-leukocyte adhesion will be evaluated using fluorescence microscopy and flow cytometry. Functional assays will investigate the role of galectin-3 in prostasome-mediated inhibition of lymphocyte proliferation and of reactive oxygen species (ROS) production in neutrophils. A potential regulatory mechanism of galectin-3 function in prostasomes involving a truncated galectin-3 variant will be investigated. We anticipate that improved understanding of immunosuppressive factors in seminal plasma and their effects on innate and adaptive immunity in the female genital tract will provide significant insights into STD/HIV transmission and pathogenesis and will have significant implications for future STD prevention strategies. ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD050540-01
Application #
6958205
Study Section
Urologic and Kidney Development and Genitourinary Diseases Study Section (UKGD)
Program Officer
Yoshinaga, Koji
Project Start
2005-08-05
Project End
2009-05-31
Budget Start
2005-08-05
Budget End
2006-05-31
Support Year
1
Fiscal Year
2005
Total Cost
$243,013
Indirect Cost
Name
University of Arkansas for Medical Sciences
Department
Biochemistry
Type
Schools of Medicine
DUNS #
122452563
City
Little Rock
State
AR
Country
United States
Zip Code
72205
Kovak, Matthew R; Saraswati, Sarika; Schoen, David J et al. (2014) Investigation of galectin-3 function in the reproductive tract by identification of binding ligands in human seminal plasma. Am J Reprod Immunol 72:403-12
Kovak, M R; Saraswati, S; Goddard, S D et al. (2013) Proteomic identification of galectin-3 binding ligands and characterization of galectin-3 proteolytic cleavage in human prostasomes. Andrology 1:682-91
Block, Ashley S; Saraswati, Sarika; Lichti, Cheryl F et al. (2011) Co-purification of Mac-2 binding protein with galectin-3 and association with prostasomes in human semen. Prostate 71:711-21
Saraswati, Sarika; Block, Ashley S; Davidson, Mari K et al. (2011) Galectin-3 is a substrate for prostate specific antigen (PSA) in human seminal plasma. Prostate 71:197-208
Jones, Jennifer L; Saraswati, Sarika; Block, Ashley S et al. (2010) Galectin-3 is associated with prostasomes in human semen. Glycoconj J 27:227-36