C-C chemokine-induced eosinophil chemotaxis during allergic airway inflammation

The production of eosinophil-specific chemotactic factors during allergic airway responses may be a pivotal event resulting in eosinophil accumulation, activation, and airway damage, Recent studies have identified specific chemokines that may play crucial roles in recruitment of eosinophils to the site of allergic reactions, In this study we have utilized an established model of schistosome egg antigen (SEA)-mediated allergic responses to examine the role of specific C-C chemokines [macrophage inflammatory protein-1 alpha (MIP-1 alpha), RANTES, and monocyte chemo-attractant protein-1 (MCP-1)] in eosinophil recruitment, We have previously identified a role for MIP-1 alpha in eosinophil accumulation in the lung and airway during allergic airway inflammation, We extend those studies using in vitro eosinophil chemotaxis to establish that both MIP-1 alpha and RANTES are potent eosinophil chemotactic factors in lungs during allergic airway responses, Morphometric analysis demonstrated a peribronchial accumulation of eosinophils within the lungs beginning at 8 h, peaking at 24 h, and plateauing at 48-96 h after allergen (SEA) challenge, Utilizing whole-lung homogenates from allergen-challenged mice, in vitro eosinophil chemotactic assays demonstrated significant increases in eosinophil chemotactic activity with 8-h lung homogenates and peak activity with samples from 24-h lung homogenates. These data correlated with the morphometric analysis of peribronchial eosinophil accumulation in situ, When lung homogenates from allergen-challenged mice were preincubated in vitro with antibodies specific for MIP-1 alpha, RANTES, or MCP-1, a significant reduction in eosinophil chemotaxis was observed with only MIP-1 alpha and RANTES neutralization, Altogether, these studies indicate that RANTES and MIP-1 alpha are major eosinophil chemotactic factors produced during allergic airway responses.