Endometriotic haptoglobin binds to peritoneal macrophages and alters their function in women with endometriosis

OBJECTIVE: To evaluate the effects of endometriotic haptoglobin on peritoneal macrophage function. DESIGN: Prospective laboratory study. SETTING: School of medicine. PATIENT(S): Twenty-three women with and without endometriosis. INTERVENTION(S): Peritoneal macrophages cultured without or with haptoglobin. MAIN OUTCOME MEASURE(S): Peritoneal macrophage haptoglobin immunoreactivity, adhesion, and interleukin-6 (IL-6) production. RESULT(S): In vivo, significantly more peritoneal macrophages from women with endometriosis bound haptoglobin and exhibited reduced adhesion compared to women without endometriosis. In vitro, haptoglobin treatment significantly decreased peritoneal macrophage adherence only in women without endometriosis; this effect was not seen in women with endometriosis, probably owing to in vivo haptoglobin saturation. Conversely, haptoglobin treatment robustly increased IL-6 production only by macrophages from women with endometriosis, suggesting differential immune response in these women. CONCLUSION(S): Endometriotic lesions synthesize and secrete a unique form of haptoglobin (endometriosis protein-I) that is up-regulated by IL-6. This study shows that haptoglobin adheres to peritoneal macrophages; decreases adhesion, which may influence phagocytic function; and up-regulates IL-6 production. Hence, a feed-forward loop is proposed whereby endometriotic lesion haptoglobin decreases macrophage phagocytic function while increasing IL-6 production, which in turn increases endometriotic haptoglobin and promotes establishment of endometriosis.