Sickle erythrocytes adhere to polymorphonuclear neutrophils and activate the neutrophil respiratory burst
Sickle erythrocytes adhere to polymorphonuclear neutrophils and activate the neutrophil respiratory burst
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DOI：
10.1182/blood.v87.10.4440.bloodjournal87104440
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发表时间：
1996-05-15
期刊：
影响因子：
20.3
通讯作者：
Coates, TD
中科院分区：
文献类型：
--
作者：
Hofstra, TC;Kalra, VK;Coates, TD
镰状细胞病（SCD）患者的血管闭塞过程是复杂的，涉及镰状红细胞（SS-RBC）、血管内皮、血浆和细胞成分之间的相互作用，中性粒细胞（PMN）在血管闭塞中的作用尚未被研究。SCD患者似乎有慢性活化的PMN。由于PMN激活的第一步是粒子识别，我们探讨了正常的PMN是否识别SS-RBC以及这种识别是否导致PMN激活。当SS-RBC在PMN单层上沉淀时，与正常红细胞相比，SS-RBC明显更多地粘附在PMN上（AA-RBC; P < 0.001）。自体血浆预孵育红细胞可显著增加SS-RBC对PMN的粘附性，但对AA-RBC无影响（P < 0.001）。当进行密度分级SS-RBC粘附时，致密SS-RBC比轻SS-RBC对PMN单层的粘附更强（P < 0.001）。为了确定这种粘附机制，我们将PMN上的IgG和Arg-Gly-Asp-Ser （RGDS）受体位点饱和。IgG抑制了致密SS-RBC的粘附，而RGDS抑制了两个部分的粘附，尽管在较轻的部分中抑制程度更大。我们通过将SS-RBC与2',7'-二氯荧光素双乙酸酯（DCF）标记的PMN孵育来测量SS-RBC对PMN的激活，与AA-RBC相比，PMN与SS-RBC孵育导致荧光显著增加。我们在这里发现PMN通过多种机制识别SS-RBC，并且这种识别导致PMN的激活，这些发现有助于理解SCD患者的血管闭塞危机，并可能具有治疗意义。(C) 1996年由美国血液病学会出版。
The vasoocclusive process in patients with sickle cell disease (SCD) is complex and involves interactions among sickle erythrocytes (SS-RBC), vascular endothelium, and plasma and cellular components, The role of neutrophils (PMN) in vasoocclusion has not been examined. Patients with SCD appear to have chronically activated PMN. Because the first step in PMN activation is particle recognition, we explored whether normal PMN recognize SS-RBC and whether this recognition results in PMN activation. When SS-RBC were allowed to settle over PMN monolayers, significantly more SS-RBC adhered to the PMN than did normal erythrocytes (AA-RBC; P < .001). Preincubation of erythrocytes with autologous plasma significantly increased the adherence of SS-RBC to PMN but had no effect on AA-RBC (P < .001). When adhesion of density fractionated SS-RBC was performed, dense SS-RBC showed greater adherence to the PMN monolayers than did light SS-RBC (P < .001). To determine mechanisms of this adhesion, IgG and Arg-Gly-Asp-Ser (RGDS) receptor sites on PMN were saturated. IgG inhibited adherence of dense SS-RBC, whereas RGDS inhibited adherence in both fractions, although to a greater extent in the light fraction, We measured SS-RBC activation of PMN by incubating SS-RBC with 2',7'-Dichloro-fluroescin Diacetate (DCF)-labeled PMN, Incubation of PMN with SS-RBC resulted in a significant increase in fluorescence compared to AA-RBC. We show here that PMN recognize SS-RBC through multiple mechanisms and that this recognition results in activation of PMN, These findings contribute to the understanding of vasoocclusive crisis in patients with SCD and may have therapeutic implications. (C) 1996 by The American Society of Hematology.