Menezes Gustavo Batista, Rezende Rafael Machado, Pereira-Silva Pedro Elias Marques, Klein André, Cara Denise Carmona, Francischi Janetti Nogueira
Laboratório de Inflamação e Dor - Instituto de Ciências Biológicas, UFMG, Brazil.
Eur J Pharmacol. 2008 Nov 19;598(1-3):118-22. doi: 10.1016/j.ejphar.2008.08.037. Epub 2008 Sep 19.
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.
使用环氧化酶（COX）2抑制剂塞来昔布或非选择性COX抑制剂吲哚美辛进行预处理，可减少脂多糖（LPS）诱导的白细胞向大鼠腹腔的迁移。研究了塞来昔布（12毫克/千克）或吲哚美辛（2毫克/千克）对体外趋化试验（Boyden小室）中由甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）诱导的中性粒细胞趋化性的影响。塞来昔布和吲哚美辛抑制了FMLP诱导的趋化性（对照组=26.6±1.45，塞来昔布=12.8±3.04，吲哚美辛=6.26±2.19个细胞/视野）。在活体显微镜观察下，使用小鼠提睾肌制剂评估微血管系统，以进一步研究细胞募集的哪个步骤受这些药物影响。塞来昔布和吲哚美辛抑制了向提睾肌注射0.05微克/千克LPS诱导的白细胞迁移。然而，塞来昔布的作用与细胞滚动和黏附减少有关，而吲哚美辛仅在抑制细胞黏附方面有效。此外，正常组织或LPS刺激组织的SC560预处理（一种COX-1选择性抑制剂）并未改变白细胞迁移或细胞黏附，但在两种情况下均增强了白细胞滚动活性。综上所述，这些结果表明：1）COX-1活性在生理条件下主要与白细胞运输有关；2）COX-2活性在血管床炎症条件下主要与细胞运输有关，提示选择性COX-2抑制剂对黏附分子表达可能有影响。
