title: The contact allergens nickel chloride and cobalt chloride directly induce expression of endothelial adhesion molecules.
abstract: Activation of vascular endothelium is a key event in the initial phase of an inflammatory reaction e.g. to contact allergens. In the present study the effect of two common contact sensitizers, NiCl2 and CoCl2, on endothelial expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1, E-selectin) was studied. NiCl2 and CoCl2 were found to upregulate these adhesion molecules on human umbilical vein endothelial cells (HUVEC) in a dose- and time-dependent manner as could be demonstrated by flow cytometry and enzyme-linked immunosorbent assay. During organ culture of foreskin samples treatment with NiCl2 led to upregulation of ELAM-1 and ICAM-1 but not VCAM-1 on microvascular endothelium. Induction of adhesion molecules by NiCl2 was found to depend on de novo mRNA and protein synthesis and could be blocked by the protein kinase inhibitor H-7 in a dose-dependent manner but not by HA-1004 and staurosporine. An autocrine IL-1-dependent mechanism mediating NiCl2 effects could be excluded. Our data demonstrate that allergens as NiCl2 and CoCl2 are capable of directly activating endothelium which is an important step in evolving inflammatory reactions and may thus be of relevance for the pathogenesis of contact hypersensitivity.
authors.affiliation: Institute of Experimental Dermatology, University of Münster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Goebeler
authors.forename: J
authors.initials: J
authors.lastname: Roth
authors.forename: G
authors.initials: G
authors.lastname: Meinardus-Hager
authors.forename: C
authors.initials: C
authors.lastname: Sorg
mesh_terms: D000485:Allergens / Q000633:toxicity*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003035:Cobalt / Q000633:toxicity*; D003877:Dermatitis, Contact; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008297:Male; D009532:Nickel / Q000633:toxicity*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1
chemical_list: D000485:Allergens; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D003035:Cobalt; C022838:nickel chloride; D009532:Nickel; C018021:cobaltous chloride