Macrophage inflammatory protein-1 alpha 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-1 alpha (MIP-1 alpha) has previously been found to be chemotactic for eosinophils, in vitro, we postulated that MIP-1 alpha was involved in the airway inflammation and more specifically in eosinophil recruitment into the airway. Initial studies demonstrated an increase in MIP-1 alpha mRNA expression at 8 h post-SEA challenge, as compared to vehicle-treated control mice. We next demonstrated a significant increase in MIP-1 alpha 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-1 alpha protein expression in airway epithelial cells, alveolar macrophages and in recruited mononuclear cell populations. Immunolocalization of MIP-1 alpha to cells within the bronchoalveolar lavage fluid demonstrated that macrophages and eosinophils stained positive for the protein. To determine the contribution of MIP-1 alpha expression to eosinophil accumulation, SEA-challenged mice were passively immunized with either neutralizing MIP-1 alpha 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-1 alpha antibodies with no effect on early neutrophil recruitment. These results suggest that the production of MIP-1 alpha, induced by an antigen-specific response, plays an important role in recruitment of eosinophils in this airway model of inflammation.
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
N W
NW
Lukacs
R M
RM
Strieter
C L
CL
Shaklee
S W
SW
Chensue
S L
SL
Kunkel
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D001483:Base Sequence; D002465:Cell Movement / Q000276:immunology*; D054407:Chemokine CCL4; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D007150:Immunohistochemistry; D019402:Macrophage Inflammatory Proteins; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D015846:Monokines / Q000096:biosynthesis / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D016133:Polymerase Chain Reaction; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D012550:Schistosoma mansoni / Q000276:immunology
D000947:Antigens, Helminth; D054407:Chemokine CCL4; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines