Parker A L, Likar L L, Dawicki D D, Rounds S
Department of Medicine, Providence Veterans Affairs Medical Center, Rhode Island, USA.
Am J Physiol. 1996 May;270(5 Pt 1):L695-703. doi: 10.1152/ajplung.1996.270.5.L695.
Previously we have shown that ATP enhances the adherence of HL-60 cells and human neutrophils to bovine pulmonary artery endothelial cells. The current investigations extend earlier findings by showing that ATP and UTP dose-dependently stimulate human neutrophil adherence to human pulmonary artery endothelial cells. We have also explore the mechanisms of ATP- and UTP-stimulated adherence. We have found that fucose, a component of selectin receptors, inhibits ATP-stimulated HL-60 cell-bovine pulmonary artery endothelial cell adhesion. Additionally, pretreatment of HL-60 cells with neuraminidase abolishes ATP enhancement. However, fucose does not affect ATP- or thrombin-induced adhesion of freshly isolated human neutrophils to human endothelial cells. Antibodies to human P-selection intercellular adhesion molecule (ICAM)-1, and the beta-subunit of CD11/CD18 do not alter ATP-induced adherence of HL-60 cells to bovine endothelial cells. Similarly, antibodies to human P-selectin and ICAM-1 do not inhibit human neutrophil-human pulmonary artery endothelial cell adhesion. The platelet-activating factor receptor antagonists, WEB-2086 and L-659,989, are effective in attenuating ATP- and UTP-stimulated adherence. Preincubation of neutrophils or human pulmonary artery endothelial cells with ATP or UTP also enhances adherence, an effect that is blocked by L-659,989. Thus platelet activating factor, associated with both neutrophils and endothelial cells, mediates ATP- and UTP-induced neutrophil adherence. ATP, released during vascular injury, may exacerbate neutrophil-endothelial cell interaction and thereby contribute to neutrophil-induced injury.
先前我们已经表明，ATP可增强HL-60细胞和人中性粒细胞与牛肺动脉内皮细胞的黏附。目前的研究扩展了早期的发现，表明ATP和UTP以剂量依赖的方式刺激人中性粒细胞与人类肺动脉内皮细胞的黏附。我们还探讨了ATP和UTP刺激黏附的机制。我们发现，岩藻糖作为选择素受体的一个组成部分，可抑制ATP刺激的HL-60细胞与牛肺动脉内皮细胞的黏附。此外，用神经氨酸酶预处理HL-60细胞可消除ATP的增强作用。然而，岩藻糖并不影响ATP或凝血酶诱导的新鲜分离的人中性粒细胞与人类内皮细胞的黏附。针对人P-选择素细胞间黏附分子（ICAM）-1以及CD11/CD18β亚基的抗体并不会改变ATP诱导的HL-60细胞与牛内皮细胞的黏附。同样，针对人P-选择素和ICAM-1的抗体也不会抑制人中性粒细胞与人类肺动脉内皮细胞的黏附。血小板活化因子受体拮抗剂WEB-2086和L-659,989可有效减弱ATP和UTP刺激的黏附。用ATP或UTP对中性粒细胞或人肺动脉内皮细胞进行预孵育也可增强黏附，而这种作用可被L-659,989阻断。因此，与中性粒细胞和内皮细胞均相关的血小板活化因子介导了ATP和UTP诱导的中性粒细胞黏附。在血管损伤期间释放的ATP可能会加剧中性粒细胞与内皮细胞的相互作用，从而导致中性粒细胞诱导的损伤。
