Sphingosine 1-Phosphate (S1P) in the Peritoneal Fluid Skews M2 Macrophage and Contributes to the Development of Endometriosis

Yosuke Ono, Takako Kawakita, Osamu Yoshino, Erina Sato, Kuniyuki Kano, Mai Ohba, Toshiaki Okuno, Masami Ito, Kaori Koga, Masako Honda, Akiko Furue, Takehiro Hiraoka, Shinichiro Wada, Takeshi Iwasa, Takehiko Yokomizo, Junken Aoki, Nagamasa Maeda, Nobuya Unno, Yutaka Osuga, Shuji Hirata
Biomedicines · 2021 · vol. 9(11) , pp. 1519 · doi:10.3390/biomedicines9111519 · PMID:34829748 · W3208732345
article OA: gold CC0 ⤵ 12 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This study found that sphingosine 1-phosphate (S1P) in peritoneal fluid, particularly during menstruation, promotes M2 macrophage polarization, IL-6 and COX-2 expression, and endometriotic lesion growth in mice.

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Abstract

Sphingosine 1-phosphate (S1P), an inflammatory mediator, is abundantly contained in red blood cells and platelets. We hypothesized that the S1P concentration in the peritoneal cavity would increase especially during the menstrual phase due to the reflux of menstrual blood, and investigated the S1P concentration in the human peritoneal fluid (PF) from 14 non-endometriosis and 19 endometriosis patients. Although the relatively small number of samples requires caution in interpreting the results, S1P concentration in the PF during the menstrual phase was predominantly increased compared to the non-menstrual phase, regardless of the presence or absence of endometriosis. During the non-menstrual phase, patients with endometriosis showed a significant increase in S1P concentration compared to controls. In vitro experiments using human intra-peritoneal macrophages (MΦ) showed that S1P stimulation biased them toward an M2MΦ-dominant condition and increased the expression of IL-6 and COX-2. An in vivo study showed that administration of S1P increased the size of the endometriotic-like lesion in a mouse model of endometriosis.

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endometriosis

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