Immunomodulatory role of C10 chemokine in a murine model of allergic bronchopulmonary aspergillosis.
The immunomodulatory role of the chemokine C10 was explored in allergic airway responses during experimental allergic bronchopulmonary aspergillosis (ABPA). The intratracheal delivery of Asperigillus fumigatus Ag into A. fumigatus-sensitized mice resulted in significantly increased levels of C10 within the bronchoalveolar lavage, and these levels peaked at 48 h after A. fumigatus challenge. In addition, C10 levels in BAL samples were greater than 5-fold higher than levels of other chemokines such as monocyte-chemoattractant protein-1, eotaxin, and macrophage-inflammatory protein-1alpha. From in vitro studies, it was evident that major pulmonary sources of C10 may have included alveolar macrophages, lung fibroblasts, and vascular smooth muscle cells. Experimental ABPA was associated with severe peribronchial eosinophilia, bronchial hyperresponsiveness, and augmented IL-13 and IgE levels. The immunoneutralization of C10 with polyclonal anti-C10 antiserum 2 h before the intratracheal A. fumigatus challenge significantly reduced the airway inflammation and hyperresponsiveness in this model of ABPA, but had no effect on IL-10 nor IgE levels. Taken together, these data suggest that C10 has a unique role in the progression of experimental ABPA.
Hogaboam
C M
CM
Departments ofPathology and Internal Medicine, Division of Pulmonary and Critical Care, University of Michigan Medical School, Ann Arbor, MI 48109, USA. hogaboam@path.med.umich.edu
Gallinat
C S
CS
Taub
D D
DD
Strieter
R M
RM
Kunkel
S L
SL
Lukacs
N W
NW
D000276:Adjuvants, Immunologic / Q000096:biosynthesis*; D000818:Animals; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D054413:Chemokine CCL11; D018932:Chemokine CCL2 / Q000032:analysis; D018925:Chemokines / Q000096:biosynthesis*; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000096:biosynthesis*; D016207:Cytokines / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D016753:Interleukin-10 / Q000032:analysis; D018793:Interleukin-13 / Q000032:analysis; D008168:Lung / Q000166:cytology / Q000276:immunology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology
D000276:Adjuvants, Immunologic; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D018925:Chemokines; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D018793:Interleukin-13; D016753:Interleukin-10; C070959:Ccl6 protein, mouse; D007073:Immunoglobulin E