In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 23, No. 8 ( 2003-08)
Abstract:
Objective— Inflammatory infiltrates and atherosclerotic lesions emerge when monocytes adhere to endothelial cells (ECs), migrate into the subendothelial space, and become macrophages (MΦs). Leukotrienes (LTs), products of 5-lipoxygenase, are powerful inflammatory mediators. 5-lipoxygenase + MΦs have been shown to increase during atherogenesis, and LT receptor (LT-R) transcripts were identified in diseased arteries. To investigate LT-Rs in cells involved in inflammation and atherogenesis, we used the in vitro models of human umbilical vein ECs (HUVECs) and monocyte-derived MΦs. Methods and Results— HUVECs primarily expressed transcripts of the cysteinyl (cys) LT 2 -R, which was strongly upregulated by interleukin-4. By contrast, MΦs predominantly expressed transcripts of the cysLT 1 -R. Calcium responses toward LTs revealed differential cysLT-R utilization by both cell types: HUVECs responded to both cysLTs, whereas MΦs preferentially responded to LTD 4 ; HUVECs, but not MΦs, were resistant toward a cysLT 1 -R antagonist, montelukast; cysLTs generated regular calcium oscillations in HUVECs that lasted 〉 60 minutes, resulting in 〉 500 oscillations per cell. By contrast, calcium elevations in MΦs returned to baseline within seconds and were nonoscillatory. Conclusions— Our data raise the possibility that MΦ-derived LTs differentially activate cysLT 2 -Rs via paracrine stimulation and cysLT 1 -Rs via autocrine and paracrine stimulation during inflammation and atherogenesis.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/01.ATV.0000082690.23131.CB
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2003
detail.hit.zdb_id:
1494427-3
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