C3a and C5a enhance granulocyte adhesion to endothelial and epithelial cell monolayers: epithelial and endothelial priming is required for C3a-induced eosinophil adhesion
C3a and C5a enhance granulocyte adhesion to endothelial and epithelial cell monolayers: epithelial and endothelial priming is required for C3a-induced eosinophil adhesion
复制标题
DOI：
10.1016/s0162-3109(99)00178-2
复制
发表时间：
2000-03-01
期刊：
影响因子：
--
通讯作者：
Hugli, TE
中科院分区：
文献类型：
--
作者：
Jagels, MA;Daffern, PJ;Hugli, TE
本文研究了过敏毒素C3 a、C5 a对嗜酸性粒细胞和中性粒细胞与人脐静脉内皮细胞（HUVEC）和原代培养的人支气管上皮细胞（HBEC）粘附的影响。检查了对白细胞和结构细胞的活性。C3 a上调β 2整合素的表达并引起嗜酸性粒细胞上L-选择素的脱落，但对中性粒细胞粘附分子的表达没有影响。C5 a上调β 2整合素并引起嗜酸性粒细胞和中性粒细胞上的L-选择素脱落。C5 a对两种细胞类型的效力是相等的;然而，这些粘附分子中的每一种的变化幅度在中性粒细胞中显著大于嗜酸性粒细胞。C3 a和C5 a都不改变HUVEC或HBEC上的ICAM-1、VCAM-1、E-选择素或P-选择素的表达。C5 a诱导嗜中性粒细胞和嗜酸性粒细胞与未刺激的HUVEC或HBEC的粘附，并且当分别用TNF-α和IFN-γ“致敏”HUVEC和HBEC时，粘附进一步增强。C3 a不能增强嗜酸性粒细胞或中性粒细胞与未致敏的HUVEC或HBEC的粘附，并且仅增强嗜酸性粒细胞与精氨酸致敏的HUVEC或HBEC的粘附。与C3 a类似，C3 a（desArg）和C3 a类似肽E7也仅增强嗜酸性粒细胞与精氨酸致敏的HUVEC和HBEC的粘附。这些结果支持过敏毒素作为白细胞特异性介质的传统观点。C3 a对嗜酸性粒细胞的特异性暗示该分子是过敏性炎症的潜在参与者。C3 a（desArg）的促粘附作用表明，该分子以前被表征为C3 a的无痉挛活性衍生物，也可能改变C3 a白细胞动力学和迁移。最后，内皮细胞的激活可能是C3 a介导的粘附的重要控制机制，可防止未受抑制的嗜酸性粒细胞粘附至未发炎的全身血管系统，（C）2000 Elsevier Science B. V.保留所有权利。
Effects of the anaphylatoxins C3a acid C5a on eosinophil and neutrophil adhesion to HUVEC and to primary culture human bronchial epithelial cells (HBEC) were investigated. Activities on both leukocytes and on structural cells were examined. C3a upregulated beta(2) integrin expression and caused shedding of L-selectin on eosinophils, but had no effect on neutrophil adhesion molecule expression. C5a upregulated beta(2) integrins and caused shedding of L-selectin on both eosinophils and neutrophils. The potency of C5a was equivalent on both cell types; however, the magnitude of the changes in each of these adhesion molecules was significantly greater in neutrophils than eosinophils, Neither C3a nor C5a altered expression of ICAM-1, VCAM-1, E-selectin or P-selectin on either HUVEC or HBEC. C5a induced adhesion of both neutrophils and eosinophils to unstimulated HUVEC or HBEC, and adhesion was further enhanced when HUVEC and HBEC were "primed" with TNF-alpha and lFN-gamma, respectively. C3a failed to enhance adhesion of either eosinophils or neutrophils to unprimed HUVEC or HBEC, and enhanced only eosinophil adhesion to cytokine-primed HUVEC or HBEC. Similar to C3a, C3a(desArg) and a C3a-analog peptide E7 also enhanced eosinophil adhesion only to cytokine-primed HUVEC and HBEC. These results support the traditional view of anaphylatoxins as leukocyte-specific mediators, The specificity of C3a for eosinophils implicates this molecule as a potential participant in allergic inflammation. The pro-adhesive effects of C3a(desArg) suggest that this molecule, previously characterized as a spasmogenically inactive derivative of C3a, may also alter C3a leukocyte dynamics and migration. Finally, activation of endothelium may represent an important control mechanism for C3a-mediated adhesion preventing unchecked eosinophil adhesion to uninflamed systemic vasculature, (C) 2000 Elsevier Science B.V. All rights reserved.