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.


METHODS
Prospective laboratory study.


METHODS
School of medicine.


METHODS
Twenty-three women with and without endometriosis.


METHODS
Peritoneal macrophages cultured without or with haptoglobin.


METHODS
Peritoneal macrophage haptoglobin immunoreactivity, adhesion, and interleukin-6 (IL-6) production.


RESULTS
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.


CONCLUSIONS
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.
Sharpe-Timms
Kathy L
KL
Department of Obstetrics and Gynecology, University of Missouri-Columbia, Columbia, Missouri 65212, USA. timmsk@health.missouri.edu
Zimmer
Randy L
RL
Ricke
Emily A
EA
Piva
Marta
M
Horowitz
Gary M
GM
D000328:Adult; D002448:Cell Adhesion; D002478:Cells, Cultured; D004715:Endometriosis / Q000378:metabolism*; D005260:Female; D006242:Haptoglobins / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D017737:Macrophages, Peritoneal / Q000502:physiology*; D010587:Phagocytosis
D006242:Haptoglobins; D015850:Interleukin-6