Carbohydrate- and CD18-dependent neutrophil adhesion to cardiac myocytes: Effects of adenosine
Carbohydrate- and CD18-dependent neutrophil adhesion to cardiac myocytes: Effects of adenosine
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DOI：
10.1016/0008-6363(96)00052-1
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发表时间：
1996-08-01
影响因子：
10.8
通讯作者：
Firestein, GS
中科院分区：
文献类型：
--
作者：
Bullough, DA;Magill, MJ;Firestein, GS
目的：腺苷抑制中性粒细胞对离体心肌细胞的粘附和损伤。在本研究中，选择素和CD 18相互作用的贡献嗜中性粒细胞-肌细胞粘附和腺苷的敏感性进行了评估。研究方法：将活化的人中性粒细胞和犬肌细胞与CD 18或选择素结合抑制剂、腺苷或两者的组合在37 ℃下孵育30-50分钟。中性粒细胞用0.1 μ M fMLP预处理10分钟以研究L-选择素非依赖性粘附。通过相差显微镜测量粘附。结果如下：抗L-选择素单克隆抗体、选择素阻断糖sialyl刘易斯（x）或甘露糖-6-磷酸以及抗CD 18或抗ICAM-1单克隆抗体均能抑制细胞粘附（84-99% P < 0.05）。CD 11 a，而不是CD 11b，负责大部分CD 18介导的结合。中性粒细胞和心肌细胞之间的L-选择素非依赖性相互作用被观察到，（40-50 min达到峰值粘附，而不是30 min），但仍受抗CD 18 mAb抑制（65 +/- 11% P < 0.05）和碳水化合物腺苷（100 nM）抑制粘附的这种晚期CD 18依赖性/L-选择素非依赖性阶段（61 +/-14%P < 0.05）。腺苷和抗-CD 18 mAb的组合是相加的，使得粘附被完全阻断（P < 0.05，与单独的任一药剂相比）。腺苷对粘附的抑制作用被A（2）拮抗剂DMPX（100 nM）阻止，并被A（2）激动剂CGS-21680（10 nM）或腺苷调节剂阿卡地辛（100 μ M）或GP 531（10 μ M）模拟。结论：中性粒细胞与心肌细胞的粘附不仅涉及L-选择素依赖性和L-选择素非依赖性的糖结合，还涉及CD 11 a/CD 18。腺苷抑制粘附干扰L-选择素独立的碳水化合物结合，并可能CD 18。
Objective: Adenosine inhibits neutrophil adhesion and injury to isolated cardiac myocytes. In the present study, the contribution of selectin and CD18 interactions to neutrophil-myocyte adhesion and their sensitivity to adenosine were assessed. Methods: Activated human neutrophils and canine myocytes were incubated with inhibitors of CD18 or selectin binding, adenosine, or combinations of both for 30-50 min at 37 degrees C. Neutrophils were pretreated with 0.1 mu M fMLP for 10 min to study L-selectin-independent adhesion. Adhesion was measured by phase contrast microscopy. Results: Anti-L-selectin mAb and the selectin-blocking carbohydrates sialyl Lewis(x) or mannose-6-phosphate as well as anti-CD18 or anti-ICAM-1 mAbs, inhibited cell adhesion (by 84-99% P < 0.05). CD11a, but not CD11b, was responsible fur most of the CD18-mediated binding. An L-selectin-independent interaction between neutrophils and cardiac myocytes was observed that was delayed (peak adhesion al 40-50 min, rather than 30 min), but still inhibited by anti-CD18 mAb (by 65 +/- 11% P < 0.05) and carbohydrates (by 87-97%, each P < 0.05), Adenosine (100 nM) inhibited this late CD18-dependent/L-selectin-independent phase of adhesion (by 61 +/- 14% P < 0.05). The combination of adenosine and anti-CD18 mAb was additive such that adhesion was completely blocked (P < 0.05, compared to either agent alone). Inhibition of adhesion by adenosine was prevented by the A(2) antagonist, DMPX (100 nM), and mimicked by the A(2) agonist, CGS-21680 (10 nM) or the adenosine regulating agents, acadesine (100 mu M) or GP531 (10 mu M). Conclusion: Neutrophil-myocyte adhesion involved both L-selectin-dependent and L-selectin-independent carbohydrate binding as well as CD11a/CD18. Inhibition of adhesion by adenosine interferes with L-selectin-independent carbohydrate binding and possibly CD18.