title: Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2.
abstract: Repertaxin is a new non-competitive allosteric blocker of interleukin-8 (CXCL8/IL-8) receptors (CXCR1/R2), which by locking CXCR1/R2 in an inactive conformation prevents receptor signaling and human polymorphonuclear leukocyte (PMN) chemotaxis. Given the unique mode of action of repertaxin it was important to examine the ability of repertaxin to inhibit a wide range of biological activities induced by CXCL8 in human leukocytes. Our results show that repertaxin potently and selectively blocked PMN adhesion to fibrinogen and CD11b up-regulation induced by CXCL8. Reduction of CXCL8-mediated PMN adhesion by repertaxin was paralleled by inhibition of PMN activation including secondary and tertiary granule release and pro-inflammatory cytokine production, whereas PMN phagocytosis of Escherichia coli bacteria was unaffected. Repertaxin also selectively blocked CXCL8-induced T lymphocyte and natural killer (NK) cell migration. These data suggest that repertaxin is a potent and specific inhibitor of a wide range of CXCL8-mediated activities related to leukocyte recruitment and functional activation in inflammatory sites.
authors.affiliation: Dompé S.p.A. Research Center, L'Aquila, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Casilli
authors.forename: Andrea
authors.initials: A
authors.lastname: Bianchini
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gloaguen
authors.forename: Leda
authors.initials: L
authors.lastname: Biordi
authors.forename: Edoardo
authors.initials: E
authors.lastname: Alesse
authors.forename: Claudio
authors.initials: C
authors.lastname: Festuccia
authors.forename: Barbara
authors.initials: B
authors.lastname: Cavalieri
authors.forename: Raffaele
authors.initials: R
authors.lastname: Strippoli
authors.forename: Maria Neve
authors.initials: MN
authors.lastname: Cervellera
authors.forename: Rosa
authors.initials: R
authors.lastname: Di Bitondo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferretti
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mainiero
authors.forename: Cinzia
authors.initials: C
authors.lastname: Bizzarri
authors.forename: Francesco
authors.initials: F
authors.lastname: Colotta
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bertini
mesh_terms: D039481:CD11b Antigen / Q000096:biosynthesis; D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors*; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D023062:Receptors, Interleukin-8A / Q000037:antagonists & inhibitors*; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D039481:CD11b Antigen; D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D013449:Sulfonamides; C490707:reparixin