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Leukotriene B4 receptor 1 is differentially expressed on peripheral T cells of steroid-sensitive and -resistant asthmatics.

ABSTRACT: Numbers of CD8(+) T cells expressing the leukotriene B4 (LTB4) receptor, BLT1, have been correlated with asthma severity.To examine the activation and numbers of BLT1-expressing peripheral blood CD4(+) and CD8(+) T cells from patients with steroid-sensitive (SS) and steroid-resistant (SR) asthma.CD4(+) and CD8(+) T cells isolated from peripheral blood of healthy human subjects and patients with SS and SR asthma were stimulated in culture with anti-CD3/anti-CD28 followed by analysis of BLT1 surface expression and cytokine production. Activation of CD8(+) T cells after ligation of BLT1 by LTB4 was monitored by changes in intracellular Ca(2+) concentrations.The number of BLT1-expressing cells was larger in patients with asthma than in controls and larger on activated CD8(+) than on CD4(+) T cells. Addition of LTB4 to activated CD8(+) T cells resulted in increases in intracellular Ca(2+) concentrations. Expansion of activated CD4(+) T cells, unlike CD8(+) T cells, was significantly decreased in the presence of corticosteroid. In patients with SS asthma, numbers of BLT1-expressing CD8(+) T cells were lower in the presence of corticosteroid, unlike in those with SR asthma in whom cell expansion was maintained. Levels of interleukin-13 were highest in cultured CD8(+) T cells, whereas interleukin-10 levels were higher in CD4(+) T cells from controls and patients with SS asthma. Interferon-? levels were lowest in patients with SR asthma.Differences in BLT1 expression, steroid sensitivity, and cytokine production were demonstrated in T lymphocytes from patients with SS and SR asthma. The LTB4-BLT1 pathway in CD8(+) cells may play an important role in asthma and serve as an important target in the treatment of patients with SR asthma.

SUBMITTER: Chung EH

PROVIDER: S-EPMC3951978 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Leukotriene B4 receptor 1 is differentially expressed on peripheral T cells of steroid-sensitive and -resistant asthmatics.

Chung Eun Hee EH Jia Yi Y Ohnishi Hiroshi H Takeda Katsuyuki K Leung Donald Y M DY Sutherland E Rand ER Dakhama Azzeddine A Martin Richard J RJ Gelfand Erwin W EW

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 20140107 3

<h4>Background</h4>Numbers of CD8(+) T cells expressing the leukotriene B4 (LTB4) receptor, BLT1, have been correlated with asthma severity.<h4>Objective</h4>To examine the activation and numbers of BLT1-expressing peripheral blood CD4(+) and CD8(+) T cells from patients with steroid-sensitive (SS) and steroid-resistant (SR) asthma.<h4>Methods</h4>CD4(+) and CD8(+) T cells isolated from peripheral blood of healthy human subjects and patients with SS and SR asthma were stimulated in culture with ...[more]

PMID: 24428972

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Project description:The movement of leukocytes into tissues is regulated by the local production of chemical mediators collectively referred to as chemoattractants. Although chemoattractants constitute a diverse array of molecules, including proteins, peptides, and lipids, they all appear to signal leukocytes through a related family of seven transmembrane-spanning G protein-coupled receptors. The eosinophil is a potent proinflammatory cell that is attracted into tissues during allergic inflammation, parasitic infection, and certain malignancies. Since the molecular mechanisms controlling eosinophil recruitment are incompletely understood, we performed a degenerate polymerase chain reaction on cDNA isolated from murine eosinophils to identify novel chemoattractant receptors. We report the isolation of a cDNA that encodes a 351-amino acid glycoprotein that is 78% identical to a human gene that has been reported to be a purinoceptor (P2Y7) and a leukotriene B4 (LTB4) receptor (BLTR). Chinese hamster ovary (CHO) cells transfected with this cDNA specifically bound [3H]LTB4 with a dissociation constant of 0.6 +/- 0.1 nM. Furthermore, LTB4 induced a dose-dependent intracellular calcium flux in transfected CHO cells. In contrast, [35S]dATP did not specifically bind to these transfectants. This mRNA was expressed at high levels in interleukin 5-exposed eosinophils, elicited peritoneal macrophages and neutrophils, and to a lesser extent interferon gamma stimulated macrophages. Low levels of expression were detected in the lung, lymph node, and spleen of unchallenged mice. Western blot analysis detected the mBLTR protein in murine eosinophils and alveolar macrophages as well as human eosinophils. In addition, elevated levels of mBLTR mRNA were found in the lungs of mice in a murine model of allergic pulmonary inflammation in a time course consistent with the influx of eosinophils. Our findings indicate that this murine receptor is an LTB4 receptor that is highly expressed on activated leukocytes, including eosinophils, and may play an important role in mediating eosinophil recruitment into inflammatory foci.

Dataset Information

Leukotriene B4 receptor 1 is differentially expressed on peripheral T cells of steroid-sensitive and -resistant asthmatics.

Publications

Leukotriene B4 receptor 1 is differentially expressed on peripheral T cells of steroid-sensitive and -resistant asthmatics.

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