Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion
Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion
复制标题
DOI：
10.1182/blood-2001-12-0289
复制
发表时间：
2003-04-15
期刊：
影响因子：
20.3
通讯作者：
Parise, LV
中科院分区：
文献类型：
--
作者：
Hines, PC;Zen, Q;Parise, LV
血管闭塞危象是镰状细胞性贫血的主要临床特征，其被认为是由镰状（SS）红细胞（RBC）粘附于血管壁引发或持续的。SS RBC，但不是未受影响的（AA）RBC，强烈粘附于血管壁的多种组分，包括层粘连蛋白。在这里，我们报告了肾上腺素和环磷酸腺苷（cAMP）的调节人SS红细胞膜通过层粘连蛋白受体，基底细胞粘附分子/路德（BCAM/Lu）的新作用。我们的数据表明，在基础条件下，外周SS RBC比AA RBC含有超过4倍的cAMP。毛喉素或应激介质肾上腺素进一步升高SS RBC中的cAMP，并以蛋白激酶A（PKA）依赖性方式增加SS RBC与层粘连蛋白的粘附，其中低密度群体是最敏感的。肾上腺素-，刺激粘附层粘连蛋白，主要通过β 2-肾上腺素能受体介导，发生在SS红细胞样本的46%的患者，并被阻断重组，可溶性BCAM/Lu，暗示，这种受体作为cAMP信号的目标。因此，这些研究证明了一种新的，快速调节SS RBC粘附的cAMP依赖性途径，并建议该途径的组成部分，特别是PKA，β 2-肾上腺素能受体，和BCAM/Lu，应进一步探讨是潜在的治疗目标，以抑制SS RBC粘附。(C)2003年，美国血液学会。
The vasoocclusive crisis is the major clinical feature of sickle cell anemia, which is believed to be initiated or sustained by sickle (SS) red blood cell (RBC) adhesion to the vascular wall. SS RBCs, but not unaffected, (AA) RBCs, adhere avidly,to multiple components of the vascular wall, including laminin. Here we report a novel role for epinephrine and cyclic adenosine monophosphate (cAMP) in the regulation of human SS RBC adhesiveness via the laminin receptor, basal cell adhesion molecule/Lutheran (BCAM/Lu). Our data demonstrate that peripheral SS RBCs contain greater than 4-fold more cAMP than AA RBCs under basal conditions. Forskolin or the stress mediator epinephrine further elevates cAMP in SS RBCs and, increases adhesion of SS RBCs to laminin in a protein kinase A (PKA)-dependent manner, with the low-density population being the most responsive. Epinephrine-, stimulated adhesion to laminin, mediated primarily via the beta2-adrenergic receptor, occurred in SS RBC samples from 46% of patients and was blocked by recombinant, soluble BCAM/Lu, implicating,this receptor as a target of cAMP signaling. Thus, these studies demonstrate a novel, rapid regulation of SS RBC adhesion by a cAMP-dependent pathway and suggest that components of this pathway, particularly PKA, the beta2-adrenergic receptor, and BCAM/Lu, should be further explored is potential therapeutic targets to inhibit SS RBC adhesion. (C) 2003 by The American Society of Hematology.