Membrane cofactor protein (CD46) in seminal plasma is a prostasome-bound form with complement regulatory activity and measles virus neutralizing activity.
Human seminal plasma contains 0.55 microgram/ml of membrane cofactor protein (MCP; CD46) of 60,000 MW. By ultracentrifugation, gel filtration and immunoelectron microscope methods, we found that the MCP in seminal plasma was associated with prostasomes. The functional properties of the prostasome-bound MCP were assessed in comparison with a recombinant soluble form, gamma MCP1, which is composed of four short consensus repeats (SCR), type C of the serine/threonine-rich domain (STC), and unknown significance (UK). The MCP in seminal plasma, although demonstrably bound to prostasomes, behaved more like the soluble form of MCP. In the absence of detergent it, together with factor I, degraded the fluid-phase ligand, methylamine-treated C3 [C3(MA)], which is insensitive under no-detergent conditions to the membrane form of MCP and factor I. Moreover, C3dg fragment was generated as a final product instead of C3bi during the incubation, indicating that the prostasomal MCP and proteases may be responsible for the C3dg generation. The prostasomes neutralized measles virus (MV) infectivity, while gamma MCP1, for the most part, did not. These results, taken together with the CD59 concentration on the prostasomes, suggest that the prostasomes are potential immunomodulators for complement activation, providing the C3- and C9-step inhibitors. The present report also reinforces the idea that there are two different forms of MCP in semen. One is located in the inner acrosomal membrane of spermatozoa, which appears through acrosomal reaction and spermatoon-egg interaction. The other is a prostasome-bound form maintaining activities sufficient to regulate complement activation and, probably, MV infection.
Kitamura
M
M
Department of Immunology, Center for Adult Diseases Osaka, Japan.
Namiki
M
M
Matsumiya
K
K
Tanaka
K
K
Matsumoto
M
M
Hara
T
T
Kiyohara
H
H
Okabe
M
M
Okuyama
A
A
Seya
T
T
D015703:Antigens, CD / Q000276:immunology*; D002850:Chromatography, Gel; D003167:Complement Activation / Q000276:immunology; D003176:Complement C3 / Q000378:metabolism*; D006801:Humans; D008297:Male; D008457:Measles / Q000276:immunology* / Q000517:prevention & control; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000276:immunology*; D016253:Microscopy, Immunoelectron; D015388:Organelles / Q000276:immunology*; D012661:Semen / Q000276:immunology*
D015703:Antigens, CD; C497857:CD46 protein, human; D003176:Complement C3; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins