Zimmerman B J, Anderson D C, Granger D N
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130.
Am J Physiol. 1992 Nov;263(5 Pt 1):G678-82. doi: 10.1152/ajpgi.1992.263.5.G678.
The objective of this study was to determine whether substance P and calcitonin gene-related peptide (CGRP), at physiologically relevant concentrations, affect leukocyte-endothelial cell adhesion. Confluent monolayers of human umbilical vein endothelial cells (HUVEC) were incubated (40 min) with freshly isolated human neutrophils in the presence or absence of substance P or CGRP (10(-11) M). Both substance P and CGRP caused a significant increase (2-fold) in neutrophil adherence to HUVEC. Monoclonal antibodies (MAb) directed against the leukocyte adhesion glycoproteins CD11/CD18 (MAb IB4) and L-selectin (MAb DREG56) did not attenuate substance P-induced adhesion. Antibodies directed against the endothelial cell adhesion molecules E-selectin (MAb CL2) and ICAM-1 (MAb R6.5) were also without effect on substance P-induced neutrophil adhesion. Similar results were obtained when either MAb IB4, DREG56, CL2, or R6.5 was coincubated with CGRP-stimulated neutrophils and endothelial cells. Phorbol 12-myristate 13-acetate-stimulated neutrophil adherence was significantly attenuated by MAb IB4, indicating that CD11/CD18 participates in this adhesion process. The results of this study indicate that 1) the neuropeptides substance P and CGRP promote neutrophil adherence to venular endothelium and 2) the neuropeptide-induced adhesion is not mediated by the adhesion molecules CD11/CD18, L-selectin, E-selectin, or ICAM-1.
本研究的目的是确定生理相关浓度的P物质和降钙素基因相关肽（CGRP）是否会影响白细胞与内皮细胞的黏附。将人脐静脉内皮细胞（HUVEC）的汇合单层细胞与新鲜分离的人中性粒细胞一起孵育（40分钟），分别加入或不加入P物质或CGRP（10⁻¹¹M）。P物质和CGRP均使中性粒细胞与HUVEC的黏附显著增加（2倍）。针对白细胞黏附糖蛋白CD11/CD18的单克隆抗体（MAb）（MAb IB4）和L-选择素（MAb DREG56）并不能减弱P物质诱导的黏附。针对内皮细胞黏附分子E-选择素（MAb CL2）和细胞间黏附分子-1（ICAM-1）的抗体（MAb R6.5）对P物质诱导的中性粒细胞黏附也没有影响。当MAb IB4、DREG56、CL2或R6.5与CGRP刺激的中性粒细胞和内皮细胞共同孵育时，也得到了类似的结果。佛波醇12-肉豆蔻酸酯13-乙酸酯刺激的中性粒细胞黏附被MAb IB4显著减弱，表明CD11/CD18参与了这一黏附过程。本研究结果表明：1）神经肽P物质和CGRP促进中性粒细胞与小静脉内皮的黏附；2）神经肽诱导的黏附不是由黏附分子CD11/CD18、L-选择素、E-选择素或ICAM-1介导的。
