HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schuh, J. M. Articles by Hogaboam, C. M. Search for Related Content PubMed PubMed Citation Articles by Schuh, J. M. Articles by Hogaboam, C. M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Medline Plus Health Information Asthma

CXCR2 Is Necessary for the Development and Persistence of Chronic Fungal Asthma in Mice¹

Department of Pathology University of Michigan Medical School, Ann Arbor, MI 48109

The role of CXCR during allergic airway and asthmatic diseases is yet to be fully characterized. Therefore, the present study addressed the role of CXCR2 during Aspergillus fumigatus-induced asthma. Mice deficient in CXCR2 (CXCR2^-/-) and wild-type counterparts (CXCR2^+/+) were sensitized to A. fumigatus Ags and challenged with A. fumigatus conidia, and the resulting allergic airway disease was monitored for up to 37 days. At days 3 and 7 after conidia, CXCR2^-/- mice exhibited significantly greater methacholine-induced airway hyperreactivity than did CXCR2^+/+ mice. In contrast, CXCR2-deficient mice exhibited significantly less airway hyperresponsiveness than the wild-type control groups at days 14 and 37 after conidia. At all times after conidia, whole lung levels of IL-4, IL-5, and eotaxin/CC chemokine ligand 11 were significantly lower in CXCR2^-/- mice than in the wild-type controls. Eosinophil and T cell, but not neutrophil, recruitment into the airways of A. fumigatus-sensitized CXCR2^-/- mice was significantly impaired compared with wild-type controls at all times after the conidia challenge. Whole lung levels of IFN-, inflammatory protein-10/CXC ligand (CXCL) 10, and monokine induced by IFN- (MIG)/CXCL9 were significantly increased in CXCR2^-/- mice compared with CXCR2^+/+ mice at various times after conidia. Interestingly, at day 3 after conidia, neutrophil recruitment and airway hyperresponsiveness in CXCR2^-/- mice was mediated by inflammatory protein-10/CXCL10 and, to a lesser degree, MIG/CXCL9. Taken together, these data suggest that CXCR2 contributes to the persistence of asthmatic disease due to A. fumigatus.

This article has been cited by other articles:

				E. Im, Y. J. Choi, C. H. Kim, C. Fiocchi, C. Pothoulakis, and S. H. Rhee The angiogenic effect of probiotic Bacillus polyfermenticus on human intestinal microvascular endothelial cells is mediated by IL-8 Am J Physiol Gastrointest Liver Physiol, November 1, 2009; 297(5): G999 - G1008. [Abstract] [Full Text] [PDF]

				Y. Okuyama-Nishida, N. Akiyama, G. Sugimori, K. Nomura, K. Ogawa, K. J. Homma, K. Sekimizu, M. Tsujimoto, and S. Natori Prevention of Death in Bacterium-Infected Mice by a Synthetic Antimicrobial Peptide, L5, through Activation of Host Immunity Antimicrob. Agents Chemother., June 1, 2009; 53(6): 2510 - 2516. [Abstract] [Full Text] [PDF]

				K. A. Cavassani, M. Ishii, H. Wen, M. A. Schaller, P. M. Lincoln, N. W. Lukacs, C. M. Hogaboam, and S. L. Kunkel TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events J. Exp. Med., October 27, 2008; 205(11): 2609 - 2621. [Abstract] [Full Text] [PDF]

				A. G. Therien, V. Bernier, S. Weicker, P. Tawa, J.-P. Falgueyret, M.-C. Mathieu, J. Honsberger, V. Pomerleau, A. Robichaud, R. Stocco, et al. Adenovirus IL-13-Induced Airway Disease in Mice: A Corticosteroid-Resistant Model of Severe Asthma Am. J. Respir. Cell Mol. Biol., July 1, 2008; 39(1): 26 - 35. [Abstract] [Full Text] [PDF]

				J. Hallgren, T. G. Jones, J. P. Abonia, W. Xing, A. Humbles, K. F. Austen, and M. F. Gurish Pulmonary CXCR2 regulates VCAM-1 and antigen-induced recruitment of mast cell progenitors PNAS, December 18, 2007; 104(51): 20478 - 20483. [Abstract] [Full Text] [PDF]

				S. R. Beaty, C. E. Rose Jr., and S.-s. J. Sung Diverse and Potent Chemokine Production by Lung CD11bhigh Dendritic Cells in Homeostasis and in Allergic Lung Inflammation J. Immunol., February 1, 2007; 178(3): 1882 - 1895. [Abstract] [Full Text] [PDF]

				C. R. Bonnett, E. J. Cornish, A. G. Harmsen, and J. B. Burritt Early Neutrophil Recruitment and Aggregation in the Murine Lung Inhibit Germination of Aspergillus fumigatus Conidia Infect. Immun., December 1, 2006; 74(12): 6528 - 6539. [Abstract] [Full Text] [PDF]

				D. W. Denning, B. R. O'Driscoll, C. M. Hogaboam, P. Bowyer, and R. M. Niven The link between fungi and severe asthma: a summary of the evidence. Eur. Respir. J., March 1, 2006; 27(3): 615 - 626. [Abstract] [Full Text] [PDF]

				S. J. Park, M. T. Wiekowski, S. A. Lira, and B. Mehrad Neutrophils Regulate Airway Responses in a Model of Fungal Allergic Airways Disease J. Immunol., February 15, 2006; 176(4): 2538 - 2545. [Abstract] [Full Text] [PDF]

				S. A. K. Harvey, E. G. Romanowski, K. A. Yates, and Y. J. Gordon Adenovirus-Directed Ocular Innate Immunity: The Role of Conjunctival Defensin-like Chemokines (IP-10, I-TAC) and Phagocytic Human Defensin-{alpha} Invest. Ophthalmol. Vis. Sci., October 1, 2005; 46(10): 3657 - 3665. [Abstract] [Full Text] [PDF]

				S. Arora, Y. Hernandez, J. R. Erb-Downward, R. A. McDonald, G. B. Toews, and G. B. Huffnagle Role of IFN-{gamma} in Regulating T2 Immunity and the Development of Alternatively Activated Macrophages during Allergic Bronchopulmonary Mycosis J. Immunol., May 15, 2005; 174(10): 6346 - 6356. [Abstract] [Full Text] [PDF]

				K. Page, V. S. Hughes, K. K. Odoms, K. E. Dunsmore, and M. B. Hershenson German Cockroach Proteases Regulate Interleukin-8 Expression via Nuclear Factor for Interleukin-6 in Human Bronchial Epithelial Cells Am. J. Respir. Cell Mol. Biol., March 1, 2005; 32(3): 225 - 231. [Abstract] [Full Text] [PDF]

				M. C. Noverr, R. M. Noggle, G. B. Toews, and G. B. Huffnagle Role of Antibiotics and Fungal Microbiota in Driving Pulmonary Allergic Responses Infect. Immun., September 1, 2004; 72(9): 4996 - 5003. [Abstract] [Full Text] [PDF]

				C. M. Hogaboam, K. Takahashi, R. A. B. Ezekowitz, S. L. Kunkel, and J. M. Schuh Mannose-binding lectin deficiency alters the development of fungal asthma: effects on airway response, inflammation, and cytokine profile J. Leukoc. Biol., May 1, 2004; 75(5): 805 - 814. [Abstract] [Full Text] [PDF]

				T. L. Ness, C. M. Hogaboam, R. M. Strieter, and S. L. Kunkel Immunomodulatory Role of CXCR2 During Experimental Septic Peritonitis J. Immunol., October 1, 2003; 171(7): 3775 - 3784. [Abstract] [Full Text] [PDF]

				N. W. Lukacs, A. L. Miller, and C. M. Hogaboam Chemokine Receptors in Asthma: Searching for the Correct Immune Targets J. Immunol., July 1, 2003; 171(1): 11 - 15. [Full Text] [PDF]

				A. L. Miller, R. M. Strieter, A. D. Gruber, S. B. Ho, and N. W. Lukacs CXCR2 Regulates Respiratory Syncytial Virus-Induced Airway Hyperreactivity and Mucus Overproduction J. Immunol., March 15, 2003; 170(6): 3348 - 3356. [Abstract] [Full Text] [PDF]

				B. Mehrad, M. Wiekowski, B. E. Morrison, S.-C. Chen, E. C. Coronel, D. J. Manfra, and S. A. Lira Transient Lung-Specific Expression of the Chemokine KC Improves Outcome in Invasive Aspergillosis Am. J. Respir. Crit. Care Med., November 1, 2002; 166(9): 1263 - 1268. [Abstract] [Full Text] [PDF]