title: Role of C-C chemokine receptors 1 and 5 and CCL3/macrophage inflammatory protein-1alpha in the cutaneous Arthus reaction: possible attenuation of their inhibitory effects by compensatory chemokine production.
abstract: The deposition of immune complexes induces an acute inflammatory response with tissue injury. Immune complex-induced tissue injury is mediated by inflammatory cell infiltration that is highly regulated by multiple chemokines. To assess the role of the chemokine receptors CCR1 and CCR5, and a ligand for these receptors CCL3/macrophage inflammatory protein-1alpha, in this pathogenic process, the reverse passive cutaneous Arthus reaction was induced in mice lacking CCR1, CCR5, or CCL3. Edema was significantly attenuated in CCR1-deficient (CCR1(-/-)) and CCL3(-/-) mice but not CCR5(-/-) mice, compared with wild-type mice. Numbers of infiltrating neutrophils and mast cells were reduced in CCL3(-/-) and CCR1(-/-) mice, respectively, compared with wild-type mice. CCR1 and CCR5 were expressed on neutrophils and mast cells. Remarkably, the intradermal mRNA expression of CCL5/RANTES, another ligand for CCR1 and CCR5, was increased in CCR5(-/-) and CCL3(-/-) mice, compared with wild-type mice, while the cutaneous CCL3 mRNA expression was augmented in CCR1(-/-) and CCR5(-/-) mice. These results indicate that CCR1, CCR5, and CCL3 cooperatively contribute to the cutaneous Arthus reaction, and also suggest that enhanced expression of CCL3 and CCL5 compensates for the loss of CCR1, CCR5, and CCL3 in the reaction.
authors.affiliation: Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Yanaba
authors.forename: Naofumi
authors.initials: N
authors.lastname: Mukaida
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Philip M
authors.initials: PM
authors.lastname: Murphy
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takehara
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D000818:Animals; D001183:Arthus Reaction / Q000276:immunology / Q000378:metabolism*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000276:immunology / Q000378:metabolism*; D004487:Edema / Q000276:immunology / Q000378:metabolism; D006470:Hemorrhage / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D010537:Peritoneum / Q000276:immunology / Q000378:metabolism; D054389:Receptors, CCR1; D019713:Receptors, CCR5 / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors
chemical_list: C515301:Ccr1 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D019402:Macrophage Inflammatory Proteins; D054389:Receptors, CCR1; D019713:Receptors, CCR5; D019707:Receptors, Chemokine