Physiologic Relevance of the Membrane Attack Complex Inhibitory Protein CD59 in Human Seminal Plasma: CD59 Is Present on Extraceilular Organelles (Prostasomes), BindsCell Membranes, and Inhibits Complement-mediated Lysis

Isabelle A. Rooney, John P. Atkinson, Elaine S. Krul, Gustav Schonfeld, Kenneth Polakoski, Jeffrey E. Saffitz, B. Paul Morgan

Research output: Contribution to journalArticlepeer-review

163 Scopus citations

Abstract

We 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.

Original languageEnglish
Pages (from-to)1409-1420
Number of pages12
JournalJournal of Experimental Medicine
Volume177
Issue number5
DOIs
StatePublished - May 1 1993

Fingerprint

Dive into the research topics of 'Physiologic Relevance of the Membrane Attack Complex Inhibitory Protein CD59 in Human Seminal Plasma: CD59 Is Present on Extraceilular Organelles (Prostasomes), BindsCell Membranes, and Inhibits Complement-mediated Lysis'. Together they form a unique fingerprint.

Cite this