This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200312-1659OCv1 169/10/1118    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, L. Articles by Kelly, E. A. B. Search for Related Content PubMed PubMed Citation Articles by Liu, L. Articles by Kelly, E. A. B.

Enhanced Generation of Helper T Type 1 and 2 Chemokines in Allergen-induced Asthma

Allergy and Immunology Section, and Pulmonary and Critical Care Section, Department of Medicine, University of Wisconsin, Madison, Wisconsin

Correspondence and requests for reprints should be addressed to Elizabeth A. (Becky) Kelly, Ph.D., Section of Pulmonary and Critical Care Medicine, 600 Highland Avenue, CSC K4/928, University of Wisconsin School of Medicine, Madison, WI 53792-9988. E-mail: eak{at}medicine.wisc.edu

Allergen-induced asthma is characterized by airway eosinophilia and recruitment of helper T (Th) Type 2 lymphocytes. We hypothesized that lymphocyte-associated chemokines contribute to allergen-induced airway inflammation. Sixteen subjects with asthma were phenotyped according to their response to inhaled antigen as single- or dual-phase responders, and then underwent bronchoscopy and segmental allergen bronchoprovocation. Bronchoalveolar lavage fluids were obtained before and 48 hours after segmental challenge with allergen to determine the cellular response and patterns of Th1 and Th2 chemokines and cytokines. Airway cells, cytokines, and lymphocyte-associated chemokines increased after segmental challenge. Th2 chemokines (thymus and activation-regulated chemokine, macrophage-derived chemokine) correlated with airway eosinophils and concentrations of interleukin-5 and -13. In contrast, airway lymphocytes correlated with both Th2 and Th1 (monokine-induced by IFN-, IFN-–inducible protein-10) chemokines. Notably, when subjects were analyzed according to the presence of a late-phase response, concentrations of both types of lymphocyte-associated chemokines were significantly greater in subjects with a dual-response phenotype. Our findings suggest that both Th2 and Th1 chemokines may be involved in allergen-induced airway inflammation. However, asthma subjects with a dual-responder phenotype have greater generation of chemokines that may lead to enhanced airway inflammation and obstruction after allergen exposure.

Key Words: bronchoalveolar lavage • chemokines • eosinophils • late-phase response • helper T Type 1/helper T Type 2 cells

This article has been cited by other articles:

				M. C. Siracusa, J. J. Reece, J. F. Urban Jr., and A. L. Scott Dynamics of lung macrophage activation in response to helminth infection J. Leukoc. Biol., December 1, 2008; 84(6): 1422 - 1433. [Abstract] [Full Text] [PDF]

				M. W. Johansson, E. A. B. Kelly, W. W. Busse, N. N. Jarjour, and D. F. Mosher Up-Regulation and Activation of Eosinophil Integrins in Blood and Airway after Segmental Lung Antigen Challenge J. Immunol., June 1, 2008; 180(11): 7622 - 7635. [Abstract] [Full Text] [PDF]

				S. B. Su, R. S. Grajewski, D. Luger, R. K. Agarwal, P. B. Silver, J. Tang, J. Tuo, C.-C. Chan, and R. R. Caspi Altered Chemokine Profile Associated with Exacerbated Autoimmune Pathology under Conditions of Genetic Interferon-{gamma} Deficiency Invest. Ophthalmol. Vis. Sci., October 1, 2007; 48(10): 4616 - 4625. [Abstract] [Full Text] [PDF]

				L. Y. Liu, M. E. Bates, N. N. Jarjour, W. W. Busse, P. J. Bertics, and E. A. B. Kelly Generation of Th1 and Th2 Chemokines by Human Eosinophils: Evidence for a Critical Role of TNF-{alpha} J. Immunol., October 1, 2007; 179(7): 4840 - 4848. [Abstract] [Full Text] [PDF]

				M. M. Monick, L. S. Powers, I. Hassan, D. Groskreutz, T. O. Yarovinsky, C. W. Barrett, E. M. Castilow, D. Tifrea, S. M. Varga, and G. W. Hunninghake Respiratory Syncytial Virus Synergizes with Th2 Cytokines to Induce Optimal Levels of TARC/CCL17 J. Immunol., August 1, 2007; 179(3): 1648 - 1658. [Abstract] [Full Text] [PDF]

				S. Y. Thomas, A. Banerji, B. D. Medoff, C. M. Lilly, and A. D. Luster Multiple Chemokine Receptors, Including CCR6 and CXCR3, Regulate Antigen-Induced T Cell Homing to the Human Asthmatic Airway J. Immunol., August 1, 2007; 179(3): 1901 - 1912. [Abstract] [Full Text] [PDF]

				I. H. Heijink, P. Marcel Kies, A. J. M. van Oosterhout, D. S. Postma, H. F. Kauffman, and E. Vellenga Der p, IL-4, and TGF-beta Cooperatively Induce EGFR-Dependent TARC Expression in Airway Epithelium Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 351 - 359. [Abstract] [Full Text] [PDF]

				N. L. Korpi-Steiner, M. E. Bates, W.-M. Lee, D. J. Hall, and P. J. Bertics Human rhinovirus induces robust IP-10 release by monocytic cells, which is independent of viral replication but linked to type I interferon receptor ligation and STAT1 activation J. Leukoc. Biol., December 1, 2006; 80(6): 1364 - 1374. [Abstract] [Full Text] [PDF]

				A M Singh and W W Busse Asthma exacerbations {middle dot} 2: Aetiology Thorax, September 1, 2006; 61(9): 809 - 816. [Abstract] [Full Text] [PDF]

				L. Woodman, A. Sutcliffe, D. Kaur, M. Berry, P. Bradding, I. D. Pavord, and C. E. Brightling Chemokine Concentrations and Mast Cell Chemotactic Activity in BAL Fluid in Patients With Eosinophilic Bronchitis and Asthma, and in Normal Control Subjects. Chest, August 1, 2006; 130(2): 371 - 378. [Abstract] [Full Text] [PDF]

				A Sutcliffe, D Kaur, S Page, L Woodman, C L Armour, M Baraket, P Bradding, J M Hughes, and C E Brightling Mast cell migration to Th2 stimulated airway smooth muscle from asthmatics Thorax, August 1, 2006; 61(8): 657 - 662. [Abstract] [Full Text] [PDF]

				W. W. Busse, A. Wanner, K. Adams, H. Y. Reynolds, M. Castro, B. Chowdhury, M. Kraft, R. J. Levine, S. P. Peters, and E. J. Sullivan Investigative Bronchoprovocation and Bronchoscopy in Airway Diseases Am. J. Respir. Crit. Care Med., October 1, 2005; 172(7): 807 - 816. [Abstract] [Full Text] [PDF]

				J. Wu, M. Kobayashi, E. A. Sousa, W. Liu, J. Cai, S. J. Goldman, A. J. Dorner, S. J. Projan, M. S. Kavuru, Y. Qiu, et al. Differential Proteomic Analysis of Bronchoalveolar Lavage Fluid in Asthmatics following Segmental Antigen Challenge Mol. Cell. Proteomics, September 1, 2005; 4(9): 1251 - 1264. [Abstract] [Full Text] [PDF]

				J. C. L. Spurrell, S. Wiehler, R. S. Zaheer, S. P. Sanders, and D. Proud Human airway epithelial cells produce IP-10 (CXCL10) in vitro and in vivo upon rhinovirus infection Am J Physiol Lung Cell Mol Physiol, July 1, 2005; 289(1): L85 - L95. [Abstract] [Full Text] [PDF]

				L. Fabbri, S. P. Peters, I. Pavord, S. E. Wenzel, S. C. Lazarus, W. MacNee, F. Lemaire, and E. Abraham Allergic Rhinitis, Asthma, Airway Biology, and Chronic Obstructive Pulmonary Disease in AJRCCM in 2004 Am. J. Respir. Crit. Care Med., April 1, 2005; 171(7): 686 - 698. [Full Text] [PDF]

				A. P. Kaplan A new mechanism for immunologic initiation of asthma PNAS, February 1, 2005; 102(5): 1267 - 1268. [Full Text] [PDF]

				C. Pechlaner Patient Outcome of Invasive Experiments Am. J. Respir. Crit. Care Med., November 1, 2004; 170(9): 1034 - 1034. [Full Text] [PDF]

				E. A. Kelly, N. N. Jarjour, W. W. Busse, and L. Liu Patient Outcome of Invasive Experiments Am. J. Respir. Crit. Care Med., November 1, 2004; 170(9): 1034 - 1034. [Full Text] [PDF]