title: Signal transduction pathways involved in macrophage migration induced by peritoneal fluid chemotactic factors in stages I and II endometriosis.
abstract: OBJECTIVE
  To explore the role of G-protein coupled signaling pathways in activation of macrophage migration in endometriosis stages I and II.
  
  
  METHODS
  Case controlled study.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Fifteen patients undergoing laparoscopy for elective sterilization (n = 5) or for diagnosis of endometriosis stages I and II associated with infertility (n = 10).
  
  
  METHODS
  Peritoneal fluid samples were collected during laparoscopy.
  
  
  METHODS
  Macrophage migration induced by peritoneal fluid from patients with endometriosis stages I and II (PF SI-II) and potential G-protein coupled receptors and second messengers involved in macrophage activation.
  
  
  RESULTS
  Potential G-protein coupled receptors and second messengers involved in macrophage activation were evaluated after incubation of U-937 cells differentiated into macrophages with inhibitors of phospholipase A and C, adenylate cyclase, and protein kinase A and C. Macrophage chemotactic activity induced by PF SI-II was inhibited in the presence of a phospholipase C and A2 inhibitor (IC50= 30 microM) and after treatment with myristoylated protein kinase C peptide inhibitor (50 nM). An increase in inositol phosphate (IP3) was also observed in macrophages exposed to PF SI-II. Activation of multiple G-proteins in macrophages was examined after exposure of cells to PF SI-II in the presence and absence of Bordettela pertussis and cholera toxins. No effect on macrophage migration was observed.
  
  
  CONCLUSIONS
  Macrophage chemotaxis induced by PF SI-II appears to involve activation of pertussis toxin-insensitive G-protein coupled receptors in macrophages. Our data suggest that these events lead to subsequent activation of phospholipases followed by generation of IP3 and potential mobilization of intracellular Ca2+. Subsequent phosphorylation of target proteins by protein kinase C may regulate the chemotactic responses. The adenylate cyclase pathway does not appear to play a role in this process.
authors.affiliation: Endocrinology Department, Women's Health Research Institute, Wyeth Pharmaceuticals, Collegeville, Pennsylvania 19426, USA. perezm1@war.wyeth.com
authors.forename: Maria Claudia
authors.initials: MC
authors.lastname: Perez
authors.forename: Peter V N
authors.initials: PV
authors.lastname: Bodine
authors.forename: Maria C
authors.initials: MC
authors.lastname: Leiva
authors.forename: Keith B
authors.initials: KB
authors.lastname: Isaacson
authors.forename: Barry S
authors.initials: BS
authors.lastname: Komm
mesh_terms: D001202:Ascitic Fluid / Q000378:metabolism*; D016022:Case-Control Studies; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D002630:Chemotactic Factors / Q000502:physiology*; D004715:Endometriosis / Q000145:classification / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
chemical_list: D002630:Chemotactic Factors; D004791:Enzyme Inhibitors; D011956:Receptors, Cell Surface; D010741:Phospholipases A; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins