Angiotensin II up-regulates CX3CR1 expression in THP-1 monocytes: impact on vascular inflammation and atherogenesis.
The potential regulatory effect of angiotensins on circulating mononuclear cell activation and migration has not yet been thoroughly evaluated. Using flow cytometry we assessed the possible effect of angiotensin I and II on the expression of CX3CR1 and a single representative of each major chemokine family (CCR5 and CXCR4) in THP-1 monocytes, Jurcat T lymphocytes and primary monocytes-isolated from healthy donors. Fluorescence intensity and the rate of chemokine-positive cells was measured in naïve cells and cells treated with angiotensin I and II. Neither angiotensin I nor angiotensin II exhibited any effect on fluorescence intensity and the rate of CX3CR1-, CCR5- and CXCR4-positive cells in primary peripheral blood mononuclear cells and Jurkat T cells. However, angiotensin II significantly increased the rate of CX3CR1-positive THP-1 cells. This effect was not attenuated by the pre-incubation of THP-1 cells with the AT-1 receptor blocker losartan, suggesting that this was not an AT-1-mediated effect. Angiotensin I and II had no effect on fluorescence intensity and the rate of CCR5- and CXCR4-positive THP-1 cells. In conclusion, angiotensin II increases the rate of CX3CR1-positive THP-1 cells. By extrapolating this in vitro observation to disease mechanisms, we speculate that angiotensin II induces up-regulation of CX3CR1 and promotes firm adhesion of circulation CX3CR1-positive monocytes on CX3CL1 expressing endothelial cells inducing vascular inflammation and atherogenesis.
Apostolakis
Stavros
S
Department of Clinical Virology, Faculty of Medicine, University of Crete, Heraklion, Greece.
Vlata
Zacharenia
Z
Vogiatzi
Konstantina
K
Krambovitis
Elias
E
Spandidos
Demetrios A
DA
D000803:Angiotensin I / Q000378:metabolism / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers; D050197:Atherosclerosis / Q000378:metabolism*; D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D054428:Chemokine CX3CL1 / Q000096:biosynthesis; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D019169:Jurkat Cells; D019808:Losartan / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D019713:Receptors, CCR5 / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D014657:Vasculitis / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; C527276:CXCR4 protein, human; D054428:Chemokine CX3CL1; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000803:Angiotensin I; D019808:Losartan