Neuropeptides promote neutrophil adherence to endothelial cell monolayers.
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.
D000911:Antibodies, Monoclonal; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D003584:Cytological Techniques; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D013755:Tetradecanoylphorbol Acetate