title: Contrasting roles for RANTES and macrophage inflammatory protein-1 alpha (MIP-1 alpha) in a murine model of allergic peritonitis.
abstract: Cell accumulation and CC chemokine production were assessed in the peritoneal cavity of ovalbumin (OVA)-sensitized mice following antigen challenge. Intraperitoneal challenge with OVA induced a significant eosinophil influx from 6 h post-challenge with increased numbers persisting at 24 h. At 6 h there was also a marked presence of neutrophils. Messenger RNA expression and protein levels for the chemokines RANTES and MIP-1 alpha were measured in the cell pellets and supernatants, respectively, from peritoneal washes following OVA challenge. RANTES mRNA was detected from 2 h to 4 h following OVA injection, whereas mRNA for MIP-1 alpha was only detectable at 4 h. RANTES protein was first detected from 4 h after OVA injection and by 24 h the protein levels had increased further. Basal levels of MIP-1 alpha were detected in peritoneal washes. These levels peaked at 2 h after OVA challenge and rapidly declined to basal levels by 6 h. A functional role for the chemokines was assessed using neutralizing polyclonal antibodies. Co-injection of OVA with anti-RANTES antibodies resulted in a significant inhibition of eosinophil infiltration into the cavity at 6 h and 24 h (63% and 52% inhibition, respectively) without significantly influencing the number of neutrophils present. In contrast, injection of anti-MIP-1 alpha antibodies only inhibited neutrophil migration at the 6 h time point by 44% without significantly affecting the accumulation of eosinophils. These results demonstrate an important role for RANTES in mediating eosinophil influx in allergic inflammation and a contrasting role for MIP-1 alpha in mediating neutrophil recruitment.
authors.affiliation: Department of Biochemical Pharmacology, The William Harvey Research Institute, St Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Das
authors.forename: M N
authors.initials: MN
authors.lastname: Ajuebor
authors.forename: R J
authors.initials: RJ
authors.lastname: Flower
authors.forename: M
authors.initials: M
authors.lastname: Perretti
authors.forename: S R
authors.initials: SR
authors.lastname: McColl
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000008:administration & dosage / Q000276:immunology / Q000502:physiology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D005260:Female; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology; D007106:Immune Sera / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D019402:Macrophage Inflammatory Proteins / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010529:Peritoneal Cavity / Q000473:pathology; D010538:Peritonitis / Q000276:immunology* / Q000473:pathology; D013997:Time Factors
chemical_list: D054407:Chemokine CCL4; D018946:Chemokine CCL5; D007106:Immune Sera; D019402:Macrophage Inflammatory Proteins; D010047:Ovalbumin