Macrophage inflammatory protein‐1α influences eosinophil recruitment in antigen‐specific airway inflammation

Allergic airway inflammation is characterized by peribronchial eosinophil accumulation within the submucosa of the airway of the lung. In the present study we have utilized a model of airway inflammation induced by intratracheal challenge with parasite (Schistosoma mansoni) egg antigen (SEA) in presensitized mice. The recruitment of neutrophils and eosinophils into the airway was found to be maximal at 8 and 48 h post challenge, respectively. Since macrophage inflammatory protein‐1α (MIP‐1α) has previously been found to be chemotactic for eosinophils, in vitro, we postulated that MIP‐1α was involved in the airway inflammation and more specifically in eosinophil recruitment into the airway. Initial studies demonstrated an increase in MIP‐1α mRNA expression at 8 h post‐SEA challenge, as compared to vehicle‐treated control mice. We next demonstrated a significant increase in MIP‐1α protein in the lungs of SEA‐challenged mice at 8 h compared to control challenged mice, correlating to the mRNA data. Immunohistochemical staining of lungs from SEA‐challenged mice demonstrated MIP‐1α protein expression in airway epithelial cells, alveolar macrophages and in recruited mononuclear cell populations. Immunolocalization of MIP‐1α to cells within the bronchoalveolar lavage fluid demonstrated that macrophages and eosinophils stained positive for the protein. To determine the contribution of MIP‐1α expression to eosinophil accumulation, SEA‐challenged mice were passively immunized with either neutralizing MIP‐1α antibodies or normal rabbit IgG, 3–4 h prior to the intratracheal SEA challenge. These studies demonstrated a > 50% decrease in eosinophil recruitment to the lungs and airway in animals receiving neutralizing MIP‐1α antibodies with no effect on early neutrophil recruitment. These results suggest that the production of MIP‐1α, induced by an antigen‐specific response, plays an important role in recruitment of eosinophils in this airway model of inflammation.