Contrasting roles for RANTES and macrophage inflammatory protein-1 alpha (MIP-1 alpha) in a murine model of allergic peritonitis

Clin Exp Immunol. 1999 Aug;117(2):223-9. doi: 10.1046/j.1365-2249.1999.00978.x.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / immunology
  • Chemokine CCL4
  • Chemokine CCL5 / administration & dosage
  • Chemokine CCL5 / immunology
  • Chemokine CCL5 / physiology*
  • Disease Models, Animal
  • Eosinophils / immunology
  • Eosinophils / pathology
  • Female
  • Hypersensitivity / immunology*
  • Hypersensitivity / pathology
  • Immune Sera / administration & dosage
  • Injections, Intraperitoneal
  • Macrophage Inflammatory Proteins / immunology
  • Macrophage Inflammatory Proteins / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils / immunology
  • Neutrophils / pathology
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Peritoneal Cavity / pathology
  • Peritonitis / immunology*
  • Peritonitis / pathology
  • Time Factors

Substances

  • Chemokine CCL4
  • Chemokine CCL5
  • Immune Sera
  • Macrophage Inflammatory Proteins
  • Ovalbumin