title: Suppression of endothelial P-selectin expression contributes to reduced cell trafficking in females: an effect independent of NO and prostacyclin.
abstract: OBJECTIVE
  Sex hormones underlie the lower incidence of cardiovascular disease in premenopausal women. Vascular inflammation is involved in the pathogenesis of several cardiovascular diseases and it has been reported that sex hormones modulate inflammatory responses but mechanisms responsible for these effects are not yet fully established. Herein, we assessed whether sex differences in leukocyte recruitment might exist and investigated the underlying mechanisms involved in this response.
  
  
  RESULTS
  Treatment with interleukin-1β (IL-1β) or tumor necrosis factor-α caused leukocyte rolling, adhesion, and emigration in mesenteric postcapillary venules in vivo that was substantially reduced in female mice compared with male mice; this difference was abolished by ovariectomy and partially restored by estrogen replacement. Deletion of endothelial nitric oxide (NO) synthase or cyclooxygenase-1 alone or in combination did not alter the leukocyte recruitment in IL-1β-treated females but significantly enhanced this response in male mice. Treatment of murine pulmonary endothelial cells with IL-1β increased expression of P-selectin in male but not female cells.
  
  
  CONCLUSIONS
  We have demonstrated a profound estrogen-dependent and NO and prostacyclin-independent suppression of leukocyte recruitment in females.
authors.affiliation: Department of Pharmacology, University College London, London, UK.
authors.forename: Inmaculada C
authors.initials: IC
authors.lastname: Villar
authors.forename: Ramona S
authors.initials: RS
authors.lastname: Scotland
authors.forename: Rayomand S
authors.initials: RS
authors.lastname: Khambata
authors.forename: Melissa
authors.initials: M
authors.lastname: Chan
authors.forename: Johan
authors.initials: J
authors.lastname: Duchene
authors.forename: Andre L
authors.initials: AL
authors.lastname: Sampaio
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Hobbs
authors.forename: Amrita
authors.initials: A
authors.lastname: Ahluwalia
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000172:deficiency / Q000235:genetics; D015536:Down-Regulation; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D004967:Estrogens / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D015918:Infusion Pumps, Implantable; D053583:Interleukin-1beta / Q000378:metabolism; D036904:Leukocyte Rolling; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000235:genetics; D010052:Ovariectomy; D019007:P-Selectin / Q000378:metabolism*; D012737:Sex Factors; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018925:Chemokines; D004967:Estrogens; D053583:Interleukin-1beta; D008565:Membrane Proteins; D019007:P-Selectin; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D011464:Epoprostenol; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D051545:Cyclooxygenase 1; C496512:Ptgs1 protein, mouse