title: The cutaneous reverse Arthus reaction requires intercellular adhesion molecule 1 and L-selectin expression.
abstract: The deposition of immune complexes (IC) induces an acute inflammatory response with tissue injury. IC-induced inflammation is mediated by inflammatory cell infiltration, a process highly regulated by expression of multiple adhesion molecules. To assess the role of L-selectin and ICAM-1 in this pathogenetic process, the cutaneous reverse passive Arthus reaction was examined in mice lacking L-selectin (L-selectin(-/-)), ICAM-1 (ICAM-1(-/-)), or both (L-selectin/ICAM-1(-/-)). Edema and hemorrhage, which peaked 4 and 8 h after IC challenge, respectively, were significantly reduced in L-selectin(-/-), ICAM-1(-/-), and L-selectin/ICAM-1(-/-) mice compared with wild-type littermates. In general, edema and hemorrhage were more significantly inhibited in ICAM-1(-/-) mice than in L-selectin(-/-) mice, but were most significantly reduced in L-selectin/ICAM-1(-/-) mice compared with ICAM-1(-/-) or L-selectin(-/-) mice. Decreased edema and hemorrhage correlated with reduced neutrophil and mast cell infiltration in all adhesion molecule-deficient mice, but leukocyte infiltration was most affected in L-selectin/ICAM-1(-/-) mice. Reduced neutrophil and mast cell infiltration was also observed for all mutant mice in the peritoneal Arthus reaction. Furthermore, cutaneous TNF-alpha production was inhibited in each deficient mouse, which paralleled the reductions in cutaneous inflammation. These results indicate that ICAM-1 and L-selectin cooperatively contribute to the cutaneous Arthus reaction by regulating neutrophil and mast cell recruitment and suggest that ICAM-1 and L-selectin are therapeutic targets for human IC-mediated disease.
authors.affiliation: Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kaburagi
authors.forename: Minoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nagaoka
authors.forename: Yuka
authors.initials: Y
authors.lastname: Shimada
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Hamaguchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Komura
authors.forename: Eriko
authors.initials: E
authors.lastname: Saito
authors.forename: Koichi
authors.initials: K
authors.lastname: Yanaba
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takehara
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kadono
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Steeber
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D000818:Animals; D001183:Arthus Reaction / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018821:CD18 Antigens / Q000096:biosynthesis; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D004487:Edema / Q000235:genetics / Q000276:immunology; D006470:Hemorrhage / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000008:administration & dosage; D007271:Injections, Intradermal; D007274:Injections, Intraperitoneal; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D019041:L-Selectin / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010529:Peritoneal Cavity / Q000473:pathology; D012867:Skin / Q000098:blood supply / Q000276:immunology* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D018821:CD18 Antigens; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin