title: Endometriotic haptoglobin binds to peritoneal macrophages and alters their function in women with endometriosis.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Missouri-Columbia, Columbia, Missouri 65212, USA. timmsk@health.missouri.edu
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Sharpe-Timms
authors.forename: Randy L
authors.initials: RL
authors.lastname: Zimmer
authors.forename: Emily A
authors.initials: EA
authors.lastname: Ricke
authors.forename: Marta
authors.initials: M
authors.lastname: Piva
authors.forename: Gary M
authors.initials: GM
authors.lastname: Horowitz
mesh_terms: 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
chemical_list: D006242:Haptoglobins; D015850:Interleukin-6