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

Cell accumulation and CC chemokine production were assessed in the peritone al cavity of ovalbumin (OVA)-sensitized mice following antigen challenge. I ntraperitoneal challenge with OVA induced a significant eosinophil influx f rom 6 h post-challenge with increased numbers persisting at 24 h. At 6 h th ere 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 fol lowing OVA challenge. RANTES mRNA was detected from 2 h to 4 h following OV A injection, whereas mRNA for MIP-1 alpha was only detectable at 4 h. RANTE S protein was first detected from 4 h after OVA injection and by 24h the pr otein levels had increased further. Basal levels of MIP-1 alpha were detect ed 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 chemoki nes was assessed using neutralizing polyclonal antibodies. Co-injection of OVA with anti-RANTES antibodies resulted in a significant inhibition of eos inophil infiltration into the cavity at 6 h and 24 h (63% and 52% inhibitio n, respectively) without significantly influencing the number of neutrophil s present. In contrast, injection of anti-MIP-1 alpha antibodies only inhib ited neutrophil migration at the 6 h time point by 44% without significantl y affecting the accumulation of eosinophils. These results demonstrate an i mportant role for RANTES in mediating eosinophil influx in allergic inflamm ation and a contrasting role for MIP-1 alpha in mediating neutrophil recrui tment.