| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Division of Allergy and Immunology, Department of Pediatrics, Children’s Hospital Medical Center, Cincinnati, OH 45229; and
Division of Biochemistry and Molecular Biology, The John Curtin School of Medical Research, Australian National University, Canberra, Australia
Eosinophil infiltration into the esophagus occurs in a wide range of diseases; however, the underlying pathophysiological mechanisms involved are largely unknown. We now report that the Th2 cytokine, IL-5, is necessary and sufficient for the induction of eosinophil trafficking to the esophagus. We show that transgenic mice overexpressing IL-5 under the control of a T cell (CD2) or a small intestinal enterocyte (fatty acid-binding protein) promoter have markedly increased eosinophil numbers in the esophagus. For example, esophageal eosinophil levels are 1.9 ± 0.9 and 121 ± 14 eosinophils/mm2 in wild-type and CD2-IL-5-transgenic mice, respectively. Consistent with this effect being mediated by a systemic mechanism, pharmacological administration of IL-5 via a miniosmotic pump in the peritoneal cavity resulted in blood and esophageal eosinophilia. To examine the role of IL-5 in oral Ag-induced esophageal eosinophilia, eosinophilic esophagitis was induced by allergen exposure in IL-5-deficient and wild-type mice. Importantly, IL-5-deficient mice were resistant to eosinophilic esophagitis. Finally, we examined the role of eotaxin when IL-5 was overproduced in vivo. Esophageal eosinophil levels in CD2-IL-5-transgenic mice were found to decrease 15-fold in the absence of the eotaxin gene; however, esophageal eosinophil numbers in eotaxin-deficient IL-5-transgenic mice still remained higher than wild-type mice. In conclusion, these studies demonstrate a central role for IL-5 in inducing eosinophil trafficking to the esophagus.
This article has been cited by other articles:
|
|
 |
|
  X. Zhu, M. Wang, C. H. Crump, and A. Mishra An imbalance of esophageal effector and regulatory T cell subsets in experimental eosinophilic esophagitis in mice Am J Physiol Gastrointest Liver Physiol, September 1, 2009; 297(3): G550 - G558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H Korsapati, A Babaei, V Bhargava, R Dohil, A Quin, and R K Mittal Dysfunction of the longitudinal muscles of the oesophagus in eosinophilic oesophagitis Gut, August 1, 2009; 58(8): 1056 - 1062. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yamada, A. Sanchez-Aguilera, E. B. Brandt, M. McBride, N. J. H. Al-Moamen, F. D. Finkelman, D. A. Williams, J. A. Cancelas, and M. E. Rothenberg FIP1L1/PDGFR{alpha} synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome Blood, September 15, 2008; 112(6): 2500 - 2507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T Sugawa, Y Fujiwara, H Yamagami, K Watanabe, T Tanigawa, M Shiba, T Watanabe, K Tominaga, N Oshitani, K Higuchi, et al. A novel rat model to determine interaction between reflux oesophagitis and bronchial asthma Gut, May 1, 2008; 57(5): 575 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mishra, J. Schlotman, M. Wang, and M. E. Rothenberg Critical role for adaptive T cell immunity in experimental eosinophilic esophagitis in mice J. Leukoc. Biol., April 1, 2007; 81(4): 916 - 924. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Mueller, T Aigner, D Neureiter, and M Stolte Eosinophil infiltration and degranulation in oesophageal mucosa from adult patients with eosinophilic oesophagitis: a retrospective and comparative study on pathological biopsy J. Clin. Pathol., November 1, 2006; 59(11): 1175 - 1180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yamada, M. E. Rothenberg, A. W. Lee, H. S. Akei, E. B. Brandt, D. A. Williams, and J. A. Cancelas The FIP1L1-PDGFRA fusion gene cooperates with IL-5 to induce murine hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL)-like disease Blood, May 15, 2006; 107(10): 4071 - 4079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Akhiani, K. Schon, and N. Lycke Vaccine-Induced Immunity against Helicobacter pylori Infection Is Impaired in IL-18-Deficient Mice J. Immunol., September 1, 2004; 173(5): 3348 - 3356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Akhiani, K. Schon, L. E. Franzen, J. Pappo, and N. Lycke Helicobacter pylori-Specific Antibodies Impair the Development of Gastritis, Facilitate Bacterial Colonization, and Counteract Resistance against Infection J. Immunol., April 15, 2004; 172(8): 5024 - 5033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Rafiee, H. Ogawa, J. Heidemann, M. S. Li, M. Aslam, T. H. Lamirand, P. J. Fisher, S. J. Graewin, M. B. Dwinell, C. P. Johnson, et al. Isolation and characterization of human esophageal microvascular endothelial cells: mechanisms of inflammatory activation Am J Physiol Gastrointest Liver Physiol, December 1, 2003; 285(6): G1277 - G1292. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
