Physiologic relevance of the membrane attack complex inhibitory protein CD59 in human seminal plasma: CD59 is present on extracellular organelles (prostasomes), binds cell membranes, and inhibits complement-mediated lysis.

Abstract

SummaryWe demonstrate here that CD59, an inhibitor of the membrane attack complex (MAC) of the complement system, is present in cell-free seminal plasma (SP) at a concentration of at least 20 #g/ml. Analyses by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, and Edman degradation indicated that this protein, SP CD59, was similar, if not identical, to CD59 isolated from erythrocyte (E) membranes (E CD59). Like purified E CD59, SP CD59 also possesses a glycosyl phosphatidyl inositol (GPI) anchor and incorporates into the membranes of heterologous cells where it inhibits lysis by the human MAC. This phenomenon could be demonstrated not only if cells were incubated with purified SP CD59 but also if unfractionated SP were used. Further, CD59 in unfractionated SP bound to washed spermatozoa, increasing their membrane content of the protein. The mechanism by which this protein retains its GPI anchor while apparently present in the fluid phase is of interest and was further investigated. Using the techniques of high-speed centrifugation, fast performance liquid chromatography fractionation, and electron microscopy, we found that all detectable SP CD59 was associated with vesicular extracellular organelles. These organelles, named "prostasomes" were previously known to be present in SP and to interact with spermatozoa, although their function was uncertain. Interaction of heterologous E with prostasomes rendered the cells more resistant to lysis by human MACs. We propose that these organelles represent a pool of CD59 from which protein lost from spermatozoa, perhaps as a result of low level complement attack or of normal membrane turnover, can be replenished.

Ascitic complement system in ovarian cancer

“…Using a Triton X-114 phase separation method, an average of 80% of AF CD59 was found to represent a form with anchor-associated phospholipid. Similarly, phospholipid-tailed CD59 has been found principally in amniotic fluid (Rooney and Morgan, 1992), seminal plasma (Rooney et al, 1993) and in milk (Hakulinen and Meri, 1995). A proportion of CD59 may also be shed in small membrane vesicles.…”

Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer

“…Proteins present on the surface of prostasomes include aminopeptidase N (CD13) (17,18) and tissue factor (CD142), a cell membraneassociated glycoprotein that serves as a receptor and essential cofactor for factors VII and VIIa of the coagulation cascade (19). The prostasomes seem to act as intercellular messengers between secretory cells of the prostate and sperm cells, transferring molecules propitious for fertilization by influencing, e.g., sperm motility (20) and exerting antibacterial, complement inhibitory, antioxidant, and immunosuppressive activities (21)(22)(23)(24).…”

The Janus-faced nature of prostasomes: their pluripotency favours the normal reproductive process and malignant prostate growth

“…59 There are reasons to believe that CD 59 is carried on the surface of the prostasomes in a GPI anchor and that spermatozoa may acquire CD 59 molecules as a result of interaction with the prostasomes. 59 Accordingly, prostasomes may represent a pool of CD 59 from which protein lost from spermatozoa, possibly as a result of normal membrane turnover or of low level complement attack, may be replenished, thus ensuring that the spermatozoa will advance in the female reproductive tract being guarded against the membrane attack complex. CD 55 (decay-accelerating factor) and CD 46 (membrane cofactor protein) are other prostasomal GPI-anchored inhibitors of complement activation.…”

“…70 Apparently, tumours use different mechanisms to evade the attack by the complement system. [71][72][73] Prostasomes contain CD 59 (protectin) on their surface 59 and on incubation with prostasomes, prostasomal CD 59, can be transferred to cells lacking CD 59 59,74 rendering these acceptor cells valid defence against a complement attack. 74 Interestingly, prostate cancer metastatic cells were found to be surrounded by prostasomes (G Sahlén et al, unpublished 2003) giving these malignant cells an advantage of survival in an otherwise hostile environment.…”