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 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 Bracke, M. Articles by Koenderman, L. Search for Related Content PubMed PubMed Citation Articles by Bracke, M. Articles by Koenderman, L.

(Journal of Leukocyte Biology. 2000;68:655-661.)
© 2000 by Society for Leukocyte Biology

In vivo priming of FcR functioning on eosinophils of allergic asthmatics

Department of Pulmonary Diseases, University Medical Center, Utrecht, The Netherlands

Correspondence: L. Koenderman, Ph.D., Department of Pulmonary Diseases, Room F02.333, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. E-mail: L.Koenderman{at}hli.azu.nl

Inflammation in allergic asthma is characterized by an influx of eosinophils and the presence of eosinophil products in the bronchial tissue. Orchestration of this inflammatory response is in part mediated by cytokines and chemoattractants, but final activation can require additional stimuli. IgA, the most abundant immunoglobulin at mucosal surfaces, is potentially a potent trigger for eosinophil activation. Previously, we have shown that binding IgA-coated targets is dependent on in vitro stimulation of cells with cytokines. Here, we demonstrate that eosinophils isolated from the blood of allergic asthmatic patients bind IgA beads independently of prior in vitro stimulation. Furthermore, we found that the proinflammatory cytokine, TNF-, is a potent enhancer of IgA binding to eosinophils from allergic asthmatics, and it does not activate FcR on eosinophils isolated from normal donors. The difference in IgA binding by FcRs on normal and patient eosinophils might be explained by the activation of different signal transduction pathways. Studying intracellular signaling, we found an enhanced basal activity of phosphatidylinositol 3-kinase (PI3K) in eosinophils derived from allergic asthmatics. Moreover, inhibition of PI3K in these cells blocked the background and the TNF--induced IgA binding completely. In summary, these data demonstrate that the responsiveness of human eosinophils to TNF- might be an important contribution for fine-tuning the allergic inflammatory reaction. Furthermore, the preactivation of PI3K results in a broader sensitivity to subsequent challenge with inflammatory cytokines.

Key Words: FCR • TNF • signal transduction • allergic asthma • PI3K

This article has been cited by other articles:

				J. E. Bakema, A. Bakker, S. de Haij, H. Honing, M. Bracke, L. Koenderman, G. Vidarsson, J. G. J. van de Winkel, and J. H. W. Leusen Inside-Out Regulation of Fc{alpha}RI (CD89) Depends on PP2A J. Immunol., September 15, 2008; 181(6): 4080 - 4088. [Abstract] [Full Text] [PDF]

				K. S. Lee, S. J. Park, S. R. Kim, K. H. Min, K. Y. Lee, Y. H. Choe, S. H. Hong, Y. R. Lee, J. S. Kim, S. J. Hong, et al. Inhibition of VEGF blocks TGF-{beta}1 production through a PI3K/Akt signalling pathway Eur. Respir. J., March 1, 2008; 31(3): 523 - 531. [Abstract] [Full Text] [PDF]

				W. ten Hove, L. A. Houben, J. A. M. Raaijmakers, L. Koenderman, and M. Bracke Rapid Selective Priming of Fc{alpha}R on Eosinophils by Corticosteroids J. Immunol., November 1, 2006; 177(9): 6108 - 6114. [Abstract] [Full Text] [PDF]

				K. S. Lee, S. R. Kim, S. J. Park, H. K. Lee, H. S. Park, K. H. Min, S. M. Jin, and Y. C. Lee Phosphatase and Tensin Homolog Deleted on Chromosome 10 (PTEN) Reduces Vascular Endothelial Growth Factor Expression in Allergen-Induced Airway Inflammation Mol. Pharmacol., June 1, 2006; 69(6): 1829 - 1839. [Abstract] [Full Text] [PDF]

				C. Pilette, S. R. Durham, J.-P. Vaerman, and Y. Sibille Mucosal Immunity in Asthma and Chronic Obstructive Pulmonary Disease: A Role for Immunoglobulin A? Proceedings of the ATS, April 1, 2004; 1(2): 125 - 135. [Abstract] [Full Text] [PDF]

				S. Myou, A. R. Leff, S. Myo, E. Boetticher, J. Tong, A. Y. Meliton, J. Liu, N. M. Munoz, and X. Zhu Blockade of Inflammation and Airway Hyperresponsiveness in Immune-sensitized Mice by Dominant-Negative Phosphoinositide 3-Kinase-TAT J. Exp. Med., November 17, 2003; 198(10): 1573 - 1582. [Abstract] [Full Text] [PDF]

				S. Sannohe, T. Adachi, K. Hamada, K. Honda, Y. Yamada, N. Saito, C-H. Cui, H. Kayaba, K. Ishikawa, and J. Chihara Upregulated response to chemokines in oxidative metabolism of eosinophils in asthma and allergic rhinitis Eur. Respir. J., June 1, 2003; 21(6): 925 - 931. [Abstract] [Full Text] [PDF]

				L. Liu, L. Hakansson, P. Ridefelt, R. C. Garcia, and P. Venge Priming of Eosinophil Migration Across Lung Epithelial Cell Monolayers and Upregulation of CD11b/CD18 Are Elicited by Extracellular Ca2+ Am. J. Respir. Cell Mol. Biol., June 1, 2003; 28(6): 713 - 721. [Abstract] [Full Text] [PDF]

				T. Persson-Dajotoy, P. Andersson, A. Bjartell, J. Calafat, and A. Egesten Expression and Production of the CXC Chemokine Growth-Related Oncogene-{alpha} by Human Eosinophils J. Immunol., May 15, 2003; 170(10): 5309 - 5316. [Abstract] [Full Text] [PDF]

				R. Hoontrakoon, H. W. Chu, S. J. Gardai, S. E. Wenzel, P. McDonald, V. A. Fadok, P. M. Henson, and D. L. Bratton Interleukin-15 Inhibits Spontaneous Apoptosis in Human Eosinophils via Autocrine Production of Granulocyte Macrophage-Colony Stimulating Factor and Nuclear Factor-kappa B Activation Am. J. Respir. Cell Mol. Biol., April 1, 2002; 26(4): 404 - 412. [Abstract] [Full Text] [PDF]

				A. Burke-Gaffney, K. Blease, A. Hartnell, and P. G. Hellewell TNF-{alpha} Potentiates C5a-Stimulated Eosinophil Adhesion to Human Bronchial Epithelial Cells: A Role for {alpha}5{beta}1 Integrin J. Immunol., February 1, 2002; 168(3): 1380 - 1388. [Abstract] [Full Text] [PDF]