P-selectin as a potential therapeutic target for endometriosis.

OBJECTIVE: To test the hypothesis that P-selectin plays a critical role in the development of endometriosis and that targeting P-selectin has therapeutic potential.

DESIGN: Prospective, randomized study.

SETTING: Academic facility.

ANIMAL(S): The first experiment used 24 each of female adult P-selectin knockout mice and C57BL/6 wild-type mice, and 96 male green fluorescent protein (GFP) transgenic mice. The second experiment used 16 female adult C57BL/6 mice.

INTERVENTION(S): In experiment 1, P-selectin knockout and wild-type mice alternately served as donors and recipients for the transplantation of endometrial tissue fragments into the peritoneal cavity to induce endometriosis. Two weeks later all four groups were each randomly divided into two equal-sized subgroups, receiving either green fluorescent protein-expressing platelets or saline infusion. In experiment 2, 2 weeks after the surgical induction of endometriosis, the mice were randomly divided into two groups, one receiving a 2-week treatment with a recombinant P-selectin protein and the other, non-immune IgG, both by intraperitoneal injection.

MAIN OUTCOME MEASURE(S): Lesion size, hotplate latency, and immunohistochemistry analysis of platelet aggregation, angiogenesis, transforming growth factor β1, α-smooth muscle actin, collagen I, and the extent of macrophage infiltration in ectopic implants. The extent of fibrosis also was evaluated in experiment 2.

RESULT(S): P-selectin deficiency significantly retarded the development of endometriosis in a mouse model of endometriosis. In addition, soluble P-selectin treatment markedly reduced the lesion size in mouse through decreased platelet aggregation and angiogenesis, improved general hyperalgesia, and reduced the extent of macrophages infiltration, resulting in reduced fibrotic tissue content.

CONCLUSION(S): Targeting P-selectin-mediated platelet adhesion onto endometriotic lesions holds promise as a novel therapeutics for treating endometriosis.