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

J Invest Dermatol. 1993 Jun;100(6):759-65. doi: 10.1111/1523-1747.ep12476328.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capillaries
  • Cell Adhesion / drug effects
  • Cell Adhesion Molecules / drug effects
  • Cell Adhesion Molecules / metabolism*
  • Cobalt / pharmacology*
  • Dermatitis, Contact / etiology*
  • E-Selectin
  • Endothelium / cytology
  • Endothelium / metabolism
  • Endothelium, Vascular / drug effects
  • Haptens / pharmacology
  • Humans
  • Intercellular Adhesion Molecule-1
  • Male
  • Nickel / pharmacology*
  • Protein Kinase Inhibitors
  • Surface Properties
  • Tachyphylaxis / physiology
  • Up-Regulation / drug effects
  • Vascular Cell Adhesion Molecule-1


  • Cell Adhesion Molecules
  • E-Selectin
  • Haptens
  • Protein Kinase Inhibitors
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Cobalt
  • nickel chloride
  • Nickel
  • cobaltous chloride