The expression of the complement regulators CD46, CD55, and CD59 by human sperm does not protect them from antisperm antibody- and complement-mediated immune injury.
OBJECTIVE
To investigate whether membrane-bound regulators of the initial (C3) and terminal (C5b-9) complement (C) pathway components are expressed on human sperm and to evaluate the protective effects of these regulators in restricting antisperm antibody and C-mediated injury.


METHODS
Sperm surface C inhibitors were quantitated by indirect immunofluorescence flow cytometry using murine monoclonal antibodies to detect C3 regulatory proteins, C3b/C4b receptor type (CR1, CD35), membrane cofactor protein (CD46), and decay-accelerating factor (CD55), and C5b-9 inhibitor, P18 (CD59) on acrosome-intact human sperm and sperm induced to undergo acrosomal loss. The susceptibility of sperm to antisperm antibody- and C-mediated immobilization was evaluated by sperm motility loss in the presence of antidecay-accelerating factor and/or anti-P18.


METHODS
University of Oklahoma Health Sciences Center, a tertiary care referral center.


RESULTS
Both decay-accelerating factor and P18 were detected on acrosome-intact and sperm induced to undergo acrosomal loss; neither expressed CR1. Membrane cofactor protein was detected on only acrosome-reacted sperm. The time course of sperm motility loss in antisperm antibody-negative sera in the presence of antidecay-accelerating factor, anti-P18, or both had a cumulative effect and brought about a time-dependent enhancement of sperm motility loss by serum C. However, sperm motility loss in C-fixing antisperm antibody-positive sera was unaffected by sperm membrane bound C3 and C5b-9 regulators.


CONCLUSIONS
The susceptibility of human sperm to antisperm antibody- and C-induced motility loss may reflect a low potency of the sperm membrane C regulators membrane cofactor protein, decay-accelerating factor, and P18 in inhibiting serum C. Therefore, the use of serum C in the traditional assay for the diagnosis of cytotoxic antisperm antibody in infertile couples may have limitations. The inefficiency of these proteins in restricting serum C activity also suggested a secondary function in restricting localized proteolytic damage at the site of fertilization.
D'Cruz
O J
OJ
Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City.
Haas
G G
GG
D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D018958:CD55 Antigens; D018957:CD59 Antigens; D003165:Complement System Proteins / Q000276:immunology*; D006801:Humans; D008297:Male; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D013081:Sperm Motility; D013094:Spermatozoa / Q000276:immunology* / Q000473:pathology; D010738:Type C Phospholipases / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D003165:Complement System Proteins; D010738:Type C Phospholipases