This Article Full Text Full Text (PDF) All Versions of this Article: 23/8/e37    most recent 01.ATV.0000082689.46538.DFv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Sjöström, M. Articles by Haeggström, J. Z. Search for Related Content PubMed PubMed Citation Articles by Sjöström, M. Articles by Haeggström, J. Z. Related Collections Health policy and outcome research Other Ethics and Policy Coagulation inhibitors Endothelium/vascular type/nitric oxide

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:e37.)
© 2003 American Heart Association, Inc.

Vascular Biology

Dominant Expression of the CysLT₂ Receptor Accounts for Calcium Signaling by Cysteinyl Leukotrienes in Human Umbilical Vein Endothelial Cells

Mattias Sjöström^*; Anne-Sofie Johansson^*; Oliver Schröder; Hong Qiu; Jan Palmblad; Jesper Z. Haeggström

From the Department of Medical Biochemistry and Biophysics (M.S., O.S., H.Q., J.Z.H.), Division of Chemistry 2, Karolinska Institutet, and the Center for Inflammation and Hematology Research (A.-S.J., J.P.), Department of Medicine, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden.

Correspondence to Jesper Z. Haeggström, MD, PhD, Department of Medical Biochemistry and Biophysics, Division of Chemistry 2, Karolinska Institutet, S-171 77 Stockholm, Sweden. E-mail jesper.haeggstrom{at}mbb.ki.se

Objective— The objective of the present study was to identify and characterize the cell-surface receptors on human umbilical vein endothelial cells (HUVECs) that transduce calcium transients elicited by cysteinyl leukotrienes (CysLTs), potent spasmogenic and proinflammatory agents with profound effects on the cardiovascular system.

Methods and Results— Using quantitative reverse transcription–polymerase chain reaction, we found that HUVECs abundantly express CysLT₂R mRNA in vast excess (>4000-fold) of CysLT₁R mRNA. Lipopolysaccharide, tumor necrosis factor-, or interleukin-1ß caused a rapid (within 30 minutes) and partially reversible suppression of CysLT₂R mRNA levels. Challenge of HUVECs with BAY u9773, a specific CysLT₂R agonist, triggered diagnostic Ca²⁺ transients. LTC₄ and LTD₄ are equipotent agonists, and their actions can be blocked by the dual-receptor antagonist BAY u9773, but not by the CysLT₁R-selective antagonist MK571.

Conclusions— HUVECs almost exclusively express the CysLT₂R. Furthermore, Ca²⁺ fluxes elicited by CysLT in these cells emanate from perturbation of the CysLT₂R, rather than the expected CysLT₁R. Hence, signaling events involving CysLT₂R might trigger functional responses involved in the critical components of LT-dependant vascular reactions, which in turn have implications for ischemic heart disease and myocardial infarction.

Key Words: leukotrienes • endothelial cells • receptors • inflammation • arteriosclerosis

This article has been cited by other articles:

				C. Thompson, A. Cloutier, Y. Bosse, C. Poisson, P. Larivee, P. P. McDonald, J. Stankova, and M. Rola-Pleszczynski Signaling by the Cysteinyl-Leukotriene Receptor 2: INVOLVEMENT IN CHEMOKINE GENE TRANSCRIPTION J. Biol. Chem., January 25, 2008; 283(4): 1974 - 1984. [Abstract] [Full Text] [PDF]

				C. Magnusson, R. Ehrnstrom, J. Olsen, and A. Sjolander An Increased Expression of Cysteinyl Leukotriene 2 Receptor in Colorectal Adenocarcinomas Correlates with High Differentiation Cancer Res., October 1, 2007; 67(19): 9190 - 9198. [Abstract] [Full Text] [PDF]

				S. B. Early, E. Barekzi, J. Negri, K. Hise, L. Borish, and J. W. Steinke Concordant Modulation of Cysteinyl Leukotriene Receptor Expression by IL-4 and IFN-{gamma} on Peripheral Immune Cells Am. J. Respir. Cell Mol. Biol., June 1, 2007; 36(6): 715 - 720. [Abstract] [Full Text] [PDF]

				G. Woszczek, L.-Y. Chen, S. Nagineni, S. Alsaaty, A. Harry, C. Logun, R. Pawliczak, and J. H. Shelhamer IFN-{gamma} Induces Cysteinyl Leukotriene Receptor 2 Expression and Enhances the Responsiveness of Human Endothelial Cells to Cysteinyl Leukotrienes J. Immunol., April 15, 2007; 178(8): 5262 - 5270. [Abstract] [Full Text] [PDF]

				H. Qiu, A.-S. Johansson, M. Sjostrom, M. Wan, O. Schroder, J. Palmblad, and J. Z. Haeggstrom Differential induction of BLT receptor expression on human endothelial cells by lipopolysacharide, cytokines, and leukotriene B4 PNAS, May 2, 2006; 103(18): 6913 - 6918. [Abstract] [Full Text] [PDF]

				Y. Hui, Y. Cheng, I. Smalera, W. Jian, L. Goldhahn, G. A. FitzGerald, and C. D. Funk Directed Vascular Expression of Human Cysteinyl Leukotriene 2 Receptor Modulates Endothelial Permeability and Systemic Blood Pressure Circulation, November 23, 2004; 110(21): 3360 - 3366. [Abstract] [Full Text] [PDF]

				T. C. Beller, A. Maekawa, D. S. Friend, K. F. Austen, and Y. Kanaoka Targeted Gene Disruption Reveals the Role of the Cysteinyl Leukotriene 2 Receptor in Increased Vascular Permeability and in Bleomycin-induced Pulmonary Fibrosis in Mice J. Biol. Chem., October 29, 2004; 279(44): 46129 - 46134. [Abstract] [Full Text] [PDF]