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 Oka, T. Articles by Ozaki, H. Search for Related Content PubMed PubMed Citation Articles by Oka, T. Articles by Ozaki, H.

Microtubule Disruption Suppresses Allergic Response through the Inhibition of Calcium Influx in the Mast Cell Degranulation Pathway¹

Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan

Mast cells are secretory cells that release their granules, which contain inflammatory mediators. Some recent data suggested that cytoskeletons play a role in this process. However, the role of microtubules in Ca²⁺ signaling has not yet been well defined. In this study, we demonstrate that the microtubule cytoskeleton is important to maintain Ca²⁺ influx in the degranulation pathway of mast cells, using the microtubule depolymerizers nocodazole and colchicine. The microtubule depolymerizers inhibited Ag-induced degranulation in RBL-2H3 cells and bone marrow-derived mast cells. When the cells were stimulated with Ag in the presence of the microtubule depolymerizers, the Ca²⁺ influx was decreased without affecting Ca²⁺ release from the endoplasmic reticulum (ER). Capacitative Ca²⁺ entry, which was induced by inhibitors of Ca²⁺-ATPase in the ER membrane, thapsigargin and cyclopiazonic acid, was also decreased by nocodazole. Fluorescent probe analysis demonstrated that nocodazole disrupted microtubule formation and changed the cytoplasmic distribution of the ER. The microtubule depolymerizers attenuated the passive cutaneous anaphylaxis reaction in back skin of Sprague Dawley rats. These results suggest that the microtubule cytoskeleton in mast cells is important to maintain Ag-induced capacitative Ca²⁺ entry, which is responsible for degranulation and the allergic response.

This article has been cited by other articles:

				J. D. Allen, Z. M. Jaffer, S.-J. Park, S. Burgin, C. Hofmann, M. A. Sells, S. Chen, E. Derr-Yellin, E. G. Michels, A. McDaniel, et al. p21-activated kinase regulates mast cell degranulation via effects on calcium mobilization and cytoskeletal dynamics Blood, March 19, 2009; 113(12): 2695 - 2705. [Abstract] [Full Text] [PDF]

				S. Wu, H. Chen, M. F. Alexeyev, J. A. C. King, T. M. Moore, T. Stevens, and R. D. Balczon Microtubule Motors Regulate ISOC Activation Necessary to Increase Endothelial Cell Permeability J. Biol. Chem., November 30, 2007; 282(48): 34801 - 34808. [Abstract] [Full Text] [PDF]

				J. T. Smyth, W. I. DeHaven, G. S. Bird, and J. W. Putney Jr Role of the microtubule cytoskeleton in the function of the store-operated Ca2+ channel activator STIM1 J. Cell Sci., November 1, 2007; 120(21): 3762 - 3771. [Abstract] [Full Text] [PDF]

				P. Mitra, C. A. Oskeritzian, S. G. Payne, M. A. Beaven, S. Milstien, and S. Spiegel Role of ABCC1 in export of sphingosine-1-phosphate from mast cells PNAS, October 31, 2006; 103(44): 16394 - 16399. [Abstract] [Full Text] [PDF]

				A. Weigert, A. M. Johann, A. von Knethen, H. Schmidt, G. Geisslinger, and B. Brune Apoptotic cells promote macrophage survival by releasing the antiapoptotic mediator sphingosine-1-phosphate Blood, September 1, 2006; 108(5): 1635 - 1642. [Abstract] [Full Text] [PDF]