title: The role of CXCR2 activity in the contact hypersensitivity response in mice.
abstract: The recruitment of polymorphonuclear neutrophil leukocytes (PMN) into a challenge site, and their subsequent activation, are thought to play a role in the elicitation of the contact hypersensitivity (CHS) response. The present study investigated the role played by CXCR2 activity in tissue PMN infiltration and subsequent triggering of CHS. Our results show that the cutaneous infiltration by PMN, induced by hapten challenge was dramatically inhibited in sensitized, CXCR2-deficient (CXCR2(-/-)) mice. Inhibition of PMN recruitment into the hapten-challenged ears of CXCR2(-/-) mice was associated with a consistent reduction of the CHS response (ear swelling) in CXCR2(-/-) mice as compared with that observed in neutropenic, wild-type (CXCR2(+/+)) mice. Prevention of skin PMN infiltration and the ear swelling response by the absence of functional CXCR2 was observed regardless of the hapten used. These data clearly suggest that CXCR2 activity plays an essential role in mediating cutaneous recruitment and activation of PMN, and thus indirectly regulates recruitment of hapten-primed T cells into challenge sites, with the subsequent elicitation of the CHS response. The role played by CXCR2 activity in the CHS response provides the rationale for testing CXCR2 inhibitors as a new therapeutic approach to skin diseases.
authors.affiliation: Research Center, Department of Preclinical Pharmacology, Dompé SpA, via Campo di Pile, 67100 L'Aquila, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Cattani
authors.forename: Anatolia
authors.initials: A
authors.lastname: Gallese
authors.forename: Marco
authors.initials: M
authors.lastname: Mosca
authors.forename: Pasquale
authors.initials: P
authors.lastname: Buanne
authors.forename: Leda
authors.initials: L
authors.lastname: Biordi
authors.forename: Sandro
authors.initials: S
authors.lastname: Francavilla
authors.forename: Gino
authors.initials: G
authors.lastname: Coletti
authors.forename: Luigi
authors.initials: L
authors.lastname: Pellegrini
authors.forename: Gabriella
authors.initials: G
authors.lastname: Melillo
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bertini
mesh_terms: D000818:Animals; D003877:Dermatitis, Contact / Q000276:immunology*; D004139:Dinitrofluorobenzene; D004487:Edema / Q000276:immunology / Q000473:pathology; D006241:Haptens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000502:physiology*; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D006241:Haptens; D023063:Receptors, Interleukin-8B; D004139:Dinitrofluorobenzene