Intrapulmonary targeting of RANTES/CCL5-responsive cells prevents chronic fungal asthma.
Regulated upon activation in normal T cells, expressed, and secreted (RANTES)/CCL5 is abundantly expressed during atopic asthma, suggesting that it is an important mediator of this disease. The contribution of intrapulmonary RANTES/CCL5-sensitive cells during Aspergillus fumigatus-induced airway disease in mice was assessed in this study. The intranasal delivery of a chimeric protein comprised of RANTES/CCL5 and a truncated version of Pseudomonas exotoxin A (RANTES-PE38) significantly attenuated serum IgE, peribronchial eosinophilia, and airway hyperreactivity when it was administered from day 0 to 15 after intratracheal conidia challenge in A. fumigatus-sensitized mice but had little effect when delivered from day 15 to 30 after conidia challenge. Intranasal RANTES-PE38 treatment enhanced macrophage recruitment and accelerated fungal clearance in the lungs of RANTES-PE38-treated mice. These data reveal a major role for RANTES/CCL5 and its receptors in the development of fungal asthma yet reveal only a modest role in the chronic remodeling of the allergic airway in this disease.
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA. janeschu@umich.edu
Jane M
JM
Schuh
Kate
K
Blease
Hilke
H
Brühl
Matthias
M
Mack
Cory M
CM
Hogaboam
D000818:Animals; D001228:Aspergillosis / Q000276:immunology / Q000517:prevention & control*; D001232:Aspergillus fumigatus / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000517:prevention & control*; D018946:Chemokine CCL5 / Q000378:metabolism*; D002908:Chronic Disease; D005434:Flow Cytometry; D020397:Goblet Cells / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice
D018946:Chemokine CCL5