title: Antibodies against the N-terminus of IL-8 receptor A inhibit neutrophil chemotaxis.
abstract: Neutrophil migration and activation are the cornerstones of the acute inflammatory response. Interleukin-8 triggers several functions of neutrophils in host defense: chemotaxis, degranulation and enzyme release, and superoxide production. Interleukin-8 is most potent as a chemoattractant, so chemotaxis is likely the most important of these functions. The effects of interleukin-8 on neutrophils are mediated through two receptors, IL-8RA and IL-8RB. To investigate the role of these receptors in neutrophil chemotaxis, we produced inhibitory antibodies to IL-8RA. These antibodies inhibit neutrophil chemotaxis toward IL-8 in vitro. These findings show that IL-8RA mediates a chemotactic signal in neutrophils and suggest that an anti-receptor strategy may be a useful approach to limit neutrophil migration in inflammation.
authors.affiliation: Seattle VA Medical Center, Washington, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Quan
authors.forename: T R
authors.initials: TR
authors.lastname: Martin
authors.forename: G B
authors.initials: GB
authors.lastname: Rosenberg
authors.forename: D C
authors.initials: DC
authors.lastname: Foster
authors.forename: T
authors.initials: T
authors.lastname: Whitmore
authors.forename: R B
authors.initials: RB
authors.lastname: Goodman
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D015936:Complement C5a / Q000494:pharmacology; D000939:Epitopes / Q000032:analysis; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D016209:Interleukin-8 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011817:Rabbits; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D014162:Transfection
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D016209:Interleukin-8; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D011994:Recombinant Proteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D002118:Calcium