title: Nitric oxide induces segregation of decay accelerating factor (DAF or CD55) from the membrane lipid-rafts and its internalization in human endometrial cells.
abstract: Recent studies suggest that DAF (decay accelerating factor), a complement regulatory protein, present in lipid rafts, is utilized by Dr fimbriated Escherichia coli for their binding and internalization. Previous studies in our laboratory have shown that NO (nitric oxide) can reduce the invasion of Dr(+) E. coli and the severity of uterine infection in pregnant rats. Also, the expression level of DAF both at the mRNA and protein levels has been shown to be reduced by NO. Therefore NO mediated down-regulation of DAF appears to be an important factor in reducing the susceptibility to E. coli infection. However, it is unclear if NO can actually modulate the membrane association of DAF and therefore initial bacterial binding to cells. We found that NO induces the delocalization of DAF from the G(M1)-rich lipid rafts. Using biochemical and cell biological approaches in a uterine epithelial cell model (Ishikawa cells), DAF accumulates in caveolae upon exposure to NO. Interaction of DAF with the caveolar protein, caveolin1, leads to their internalization by endosomes. NO-induced delocalization of DAF from the lipid raft and its accumulation in caveolae are mediated through a cGMP (cyclic guanosine monophosphate) pathway. The acute localized synthesis of NO and its influence on DAF localization may represent an important unrecognized phenomenon of host defence against Dr(+) E. coli bacteria, as well as many disease conditions that involve complement system.
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, USA.
authors.forename: Manu
authors.initials: M
authors.lastname: Banadakoppa
authors.forename: Pawel
authors.initials: P
authors.lastname: Goluszko
authors.forename: Daniel
authors.initials: D
authors.lastname: Liebenthal
authors.forename: Chandra
authors.initials: C
authors.lastname: Yallampalli
mesh_terms: D018958:CD55 Antigens / Q000378:metabolism*; D021941:Caveolae / Q000378:metabolism*; D051242:Caveolin 1 / Q000378:metabolism; D002460:Cell Line; D006152:Cyclic GMP / Q000378:metabolism; D004717:Endometrium / Q000166:cytology* / Q000382:microbiology; D011992:Endosomes / Q000378:metabolism; D005260:Female; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*
chemical_list: D018958:CD55 Antigens; D051242:Caveolin 1; D009569:Nitric Oxide; D006152:Cyclic GMP