title: Differential involvement of cyclooxygenase isoforms in neutrophil migration in vivo and in vitro.
abstract: Pretreatment using celecoxib, a cyclooxygenase (COX) 2 inhibitor, or indomethacin, a nonselective COX inhibitor, reduced lypopolyssaccharide (LPS)-induced leukocyte migration to the rat peritoneal cavity. The effect of celecoxib (12 mg/kg) or indomethacin (2 mg/kg) on neutrophil chemotaxis induced by formyl-methionyl-leucyl-phenylalanine (FMLP) in an in vitro chemotactic assay (Boyden chamber) was investigated. Celecoxib and indomethacin inhibited chemotaxis induced by FMLP (Control=26.6+/-1.45, Celecoxib=12.8+/-3.04, Indomethacin=6.26+/-2.19 cells/field). When observed under intravital microscopy, a mouse cremaster preparation was used to assess the microvasculature to further investigate which step of cell recruitment was affected by these drugs. Celecoxib and indomethacin inhibited leukocyte migration induced by 0.05 microg/kg LPS injected into the cremaster muscle. However, the effect of celecoxib was associated with reduced cell rolling and adhesion, whereas indomethacin was only effective at inhibiting cell adhesion. Furthermore, SC560 pretreatment (a COX-1 selective inhibitor) of normal or LPS-challenged tissues did not alter leukocyte migration or cell adhesion, but it did enhance leukocyte rolling activity in both cases. Taken together, these results indicate that: 1) COX-1 activity is mainly related to leukocyte traffic under physiological conditions, and 2) COX-2 activity is mainly related to cell traffic under inflammatory conditions in vascular beds, suggesting a possible effect of selective COX-2 inhibitors on the expression of adhesion molecules.
authors.affiliation: Laboratório de Inflamação e Dor - Instituto de Ciências Biológicas, UFMG, Brazil.
authors.forename: Gustavo Batista
authors.initials: GB
authors.lastname: Menezes
authors.forename: Rafael Machado
authors.initials: RM
authors.lastname: Rezende
authors.forename: Pedro Elias Marques
authors.initials: PE
authors.lastname: Pereira-Silva
authors.forename: André
authors.initials: A
authors.lastname: Klein
authors.forename: Denise Carmona
authors.initials: DC
authors.lastname: Cara
authors.forename: Janetti Nogueira
authors.initials: JN
authors.lastname: Francischi
mesh_terms: D000818:Animals; D000068579:Celecoxib; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement; D002469:Cell Separation; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000502:physiology; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D007213:Indomethacin