Angiotensin II stimulates expression of the chemokine RANTES in rat glomerular endothelial cells. Role of the angiotensin type 2 receptor.
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Angiotensin II stimulates expression of the chemokine RANTES in rat glomerular endothelial cells. Role of the angiotensin type 2 receptor. / Wolf, G; Ziyadeh, F N; Thaiss, F; Tomaszewski, J; Caron, R J; Wenzel, Ulrich; Zahner, G; Helmchen, U; Stahl, R A.
In: J CLIN INVEST, Vol. 100, No. 5, 5, 1997, p. 1047-1058.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Angiotensin II stimulates expression of the chemokine RANTES in rat glomerular endothelial cells. Role of the angiotensin type 2 receptor.
AU - Wolf, G
AU - Ziyadeh, F N
AU - Thaiss, F
AU - Tomaszewski, J
AU - Caron, R J
AU - Wenzel, Ulrich
AU - Zahner, G
AU - Helmchen, U
AU - Stahl, R A
PY - 1997
Y1 - 1997
N2 - Glomerular influx of monocytes/macrophages (M/M) occurs in many immune- and non-immune-mediated renal diseases. The mechanisms targeting M/M into the glomerulus are incompletely understood, but may involve stimulated expression of chemokines. We investigated whether angiotensin II (ANG II) induces the chemokine RANTES in cultured glomerular endothelial cells of the rat and in vivo. ANG II stimulated mRNA and protein expression of RANTES in cultured glomerular endothelial cells. The ANG II-induced RANTES protein was chemotactic for human monocytes. Surprisingly, the ANG II-stimulated RANTES expression was transduced by AT2 receptors because the AT2 receptor antagonists PD 123177 and CGP-42112A, but not an AT1 receptor blocker, abolished the induced RANTES synthesis. Intraperitoneal infusion of ANG II (500 ng/h) into naive rats for 4 d significantly stimulated glomerular RANTES mRNA and protein expression compared with solvent-infused controls. Immunohistochemistry revealed induction of RANTES protein mainly in glomerular endothelial cells and small capillaries. Moreover, ANG II- infused animals exhibited an increase in glomerular ED-1- positive cells compared with controls. Oral treatment with PD 123177 (50 mg/liter drinking water) attenuated the glomerular M/M influx without normalizing the slightly elevated systolic blood pressure caused by ANG II infusion, suggesting that the effects on blood pressure and RANTES induction can be separated. We conclude that the vasoactive peptide ANG II may play an important role in glomerular chemotaxis of M/M through local induction of the chemokine RANTES. The observation that the ANG II- mediated induction of RANTES is transduced by AT2 receptors may influence the decision as to which substances might be used for the therapeutic interference with the activity of the renin-angiotensin system.
AB - Glomerular influx of monocytes/macrophages (M/M) occurs in many immune- and non-immune-mediated renal diseases. The mechanisms targeting M/M into the glomerulus are incompletely understood, but may involve stimulated expression of chemokines. We investigated whether angiotensin II (ANG II) induces the chemokine RANTES in cultured glomerular endothelial cells of the rat and in vivo. ANG II stimulated mRNA and protein expression of RANTES in cultured glomerular endothelial cells. The ANG II-induced RANTES protein was chemotactic for human monocytes. Surprisingly, the ANG II-stimulated RANTES expression was transduced by AT2 receptors because the AT2 receptor antagonists PD 123177 and CGP-42112A, but not an AT1 receptor blocker, abolished the induced RANTES synthesis. Intraperitoneal infusion of ANG II (500 ng/h) into naive rats for 4 d significantly stimulated glomerular RANTES mRNA and protein expression compared with solvent-infused controls. Immunohistochemistry revealed induction of RANTES protein mainly in glomerular endothelial cells and small capillaries. Moreover, ANG II- infused animals exhibited an increase in glomerular ED-1- positive cells compared with controls. Oral treatment with PD 123177 (50 mg/liter drinking water) attenuated the glomerular M/M influx without normalizing the slightly elevated systolic blood pressure caused by ANG II infusion, suggesting that the effects on blood pressure and RANTES induction can be separated. We conclude that the vasoactive peptide ANG II may play an important role in glomerular chemotaxis of M/M through local induction of the chemokine RANTES. The observation that the ANG II- mediated induction of RANTES is transduced by AT2 receptors may influence the decision as to which substances might be used for the therapeutic interference with the activity of the renin-angiotensin system.
M3 - SCORING: Zeitschriftenaufsatz
VL - 100
SP - 1047
EP - 1058
JO - J CLIN INVEST
JF - J CLIN INVEST
SN - 0021-9738
IS - 5
M1 - 5
ER -