Nickel chloride and cobalt chloride, two common contact sensitizers, directly induce expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule (ELAM-1) by endothelial cells.
Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1, E-selectin) are endothelial surface molecules that play a role for leukocyte recruitment to sites of inflammation, e.g., during contact hypersensitivity. We studied the effects of sensitizing agents (2,4-dinitro-benzenesulfonic acid, metal salt haptens) and chemically related substances on endothelial adhesion molecule expression. Using flow cytometry and an enzyme-linked immunosorbent assay, NiCl2 and, to a lesser extent, CoCl2 were found to up-regulate ICAM-1, VCAM-1, and ELAM-1 expression on cultured human umbilical vein endothelium whereas the other substances tested showed no effects. Induction of adhesion molecules by NiCl2 required de novo mRNA and protein synthesis. Up-regulation could be blocked by kinase inhibitor H-7 but not staurosporine, suggesting involvement of phosphorylation events independent of protein kinase C activation. Concomitant application of NiCl2 and neutralizing antibodies to IL-1 did not block up-regulation by the hapten demonstrating that the latter did not act via an IL-1-dependent autocrine mechanism. Regarding ELAM-1 induction, pre-treatment for 24 h with NiCl2 produced hyporesponsiveness to IL-1 and TNF-alpha upon restimulation, suggesting that NiCl2 and these cytokines may partially share a common pathway of activation. In addition, analysis of cultured foreskin specimens revealed that NiCl2 may induce up-regulation of ELAM-1 on microvascular endothelium in vivo. Our data demonstrate that both Ni++ and Co++ to which simultaneous contact sensitivity is frequently observed have the ability to directly up-regulate endothelial adhesion molecules. This shared property may represent an adjuvant mechanism that promotes sensitization and elicitation events in contact hypersensitivity to these haptens.
Goebeler
M
M
Institute of Experimental Dermatology, University of Münster, Germany.
Meinardus-Hager
G
G
Roth
J
J
Goerdt
S
S
Sorg
C
C
D002196:Capillaries; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism*; D003035:Cobalt / Q000494:pharmacology*; D003877:Dermatitis, Contact / Q000209:etiology*; D019040:E-Selectin; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects; D006241:Haptens / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008297:Male; D009532:Nickel / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D013499:Surface Properties; D013618:Tachyphylaxis / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D006241:Haptens; D047428:Protein Kinase Inhibitors; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D003035:Cobalt; C022838:nickel chloride; D009532:Nickel; C018021:cobaltous chloride