Extracellular organelles (prostasomes) are immunosuppressive components of human semen

Abstract

SUMMARYNumerous reports have ascribed immunosuppressive activity to human seminal plasma and there is growing agreement ihat much of this activity can be accounted for by the very high levels of E series prostaglandins present (up to 300 /iM 19-hydroxy prostaglandin E). However not all suppressive activity is due to prostaglandin since several reports have appeared of high molecular weight active substances and we have found that stripped seminal plasma is slill effective in inhibiting the mitogeninduced proliferation of lymphocytes. In this sludy such immunosuppressive activity has been separated by molecular size I'ractionation and the activity has been lound to be particulate and corresponded to the previously reported prostascmes. These are trilaminar to multilaminar vesicles (150 nm diameter) which are secreted by the prostate. Pure preparations of proslasomes inhibited mitogen-induccd lymphoproliferation in a dose-dependont manner with a concentration of prostasomes equivalent to 4{Y'A< of thai seen in seminal fluid giving 69'y,, suppression of thymidine incorporation. The suppressive activity survived boiling and therefore was unlikely ui be due to enzymatic action associated with these organelles. Interaction with Ihe accessory cells, involved in full development ofthe lymphoproliferation induced by mitogen, was indicated and ihis possibility was supported by lhe demonstration ofa direcl effect of prostasomes on macrophage function using a mouse macrophage cell line. The proslasomes in semen may play a complementary role to the prostaglandins in neutralizing the immune defences of the female reproductive tract. This combination would allow the alloantigenie spermatozoa the best chance of achieving fertilization, but at Ihc same time leave the recipient open to any infeetion present in the semen.

Seminal prostasomes inhibit the angiogenesis activity of rat aortic rings

“…3 Prostasomes are also known to have an antioxidant effect, via stabilization of polymorphonuclear neutrophil cell membranes. 4 Proteomic analysis of prostasomes has shown them to contain more than 130 proteins, including complement inhibitors, tissue factor (CD142), and dipeptidyl peptidase IV, which has been shown to be involved in the modulation of growth factor and cytokine activity.…”

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

“…56,57 This activity accounts for a significant proportion of the immunosuppressive Janus-faced nature of prostasomes G Ronquist and BO Nilsson activity of human seminal plasma. 58 Since the prostasomes have the ability to adhere to spermatozoa, 45,48 there is the probability that the immunosuppressive effect associated with the prostasomes can be carried up the female genital tract with the spermatozoa. 58 Pure preparations of prostasomes inhibit mitogen-induced lymphoproliferation in a dose-dependent fashion with a concentration of prostasomes equivalent to 40% of that seen in seminal plasma giving 69% suppression of thymidine incorporation.…”

“…58 Since the prostasomes have the ability to adhere to spermatozoa, 45,48 there is the probability that the immunosuppressive effect associated with the prostasomes can be carried up the female genital tract with the spermatozoa. 58 Pure preparations of prostasomes inhibit mitogen-induced lymphoproliferation in a dose-dependent fashion with a concentration of prostasomes equivalent to 40% of that seen in seminal plasma giving 69% suppression of thymidine incorporation. 58 A direct effect of prostasomes on macrophage function is also apparent.…”

“…58 Pure preparations of prostasomes inhibit mitogen-induced lymphoproliferation in a dose-dependent fashion with a concentration of prostasomes equivalent to 40% of that seen in seminal plasma giving 69% suppression of thymidine incorporation. 58 A direct effect of prostasomes on macrophage function is also apparent. 56 Prostasomes bind rapidly to the leucocyte cell membrane followed by internalization of the adsorbed material.…”

“…In this matter, prostasomes, being constituents of prostate but not of seminal vesicle secretion, have been identified as inhibitors in lymphoproliferation assays. 56,58 Due to this uneven occurrence of prostasomes between the prostate gland and seminal vesicles, it is tempting to suggest that the ability of prostasomes to counteract the immune defense may play a role in the very high prevalence of prostate cancer after 50 years of age (ie after the reproductive age of most men), contrasting to the extremely low prevalence of primary cancer in the seminal vesicles lacking prostasomes in their surroundings.…”