title: Platelets play a role in the pathogenesis of the irritant reaction in mice.
abstract: The irritant reaction is a model of local inflammation that results from the epicutaneous application of a small molecule with irritating properties such as trinitrochlorobenzene (TNCB). The irritant reaction is mediated by tumor necrosis factor (TNF) and is characterized by skin edema and neutrophil (PMN) infiltration. The aim of this study was to explore the role of platelets in the pathogenesis of the irritant reaction. Mice depleted of platelets by an anti-platelet antibody showed a decrease in edema upon the application of a low dose of TNCB--chosen for causing an irritant reaction that is not complicated by intravascular fibrin deposition and hemorrhage--but no significant change in PMN infiltration. There was platelet trapping in TNCB-treated ears that was maximum between 2 and 6 h after TNCB application. Platelets lined the venular endothelium, which was intact in the absence of hemorrhage, and were not accompanied by fibrin. Mice treated with anti-TNF, anti-CD11a, anti-CD18, or anti-CD54 antibodies showed a decrease in platelet trapping, edema, and PMN infiltration. Platelets contribute to the pathogenesis of the irritant reaction and are necessary for edema to develop but not for PMN infiltration. The role of platelets implicates their early localization in the dermal venules, which depends, at least in part, on TNF and on the adhesion molecules involved in the interaction between CD11a/CD18 and CD54.
authors.affiliation: World Health Organization, Immunology Research and Training Center, Geneva, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Senaldi
authors.forename: P F
authors.initials: PF
authors.lastname: Piguet
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D018821:CD18 Antigens / Q000276:immunology; D017453:Dermatitis, Irritant / Q000209:etiology* / Q000473:pathology; D004487:Edema / Q000139:chemically induced; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009504:Neutrophils / Q000473:pathology / Q000502:physiology; D010853:Picryl Chloride / Q000008:administration & dosage; D013921:Thrombocytopenia / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000906:Antibodies; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D010853:Picryl Chloride