Eluate derived by extracorporal antibody-based immunoadsorption elevates the cytosolic Ca2+ concentration in podocytes via B2 kinin receptors
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Eluate derived by extracorporal antibody-based immunoadsorption elevates the cytosolic Ca2+ concentration in podocytes via B2 kinin receptors. / Fischer, Karl-Georg; Huber, Tobias Bruno; Henger, Anna; Fink, Edwin; Schwertfeger, Eckhard; Rump, Lars Christian; Pavenstädt, Hermann.
In: KIDNEY BLOOD PRESS R, Vol. 25, No. 6, 2002, p. 384-93.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Eluate derived by extracorporal antibody-based immunoadsorption elevates the cytosolic Ca2+ concentration in podocytes via B2 kinin receptors
AU - Fischer, Karl-Georg
AU - Huber, Tobias Bruno
AU - Henger, Anna
AU - Fink, Edwin
AU - Schwertfeger, Eckhard
AU - Rump, Lars Christian
AU - Pavenstädt, Hermann
N1 - Copyright 2002 S. Karger AG, Basel
PY - 2002
Y1 - 2002
N2 - BACKGROUND/AIM: Patients with idiopathic focal segmental glomerulosclerosis (FSGS) often develop a recurrence of the disease after kidney transplantation. In a number of FSGS patients, plasmapheresis and immunoadsorption procedures have been shown to transiently reduce proteinuria and are thought to do this by eliminating a circulating factor. Direct cellular effects of eluates from immunoadsorption procedures on podocytes, the primary target of injury in FSGS, have not yet been reported.METHODS: Eluates were derived from antibody-based immunoadsorption of a patient suffering from primary FSGS, a patient with systemic lupus erythematosus, and a healthy volunteer. The cytosolic free Ca(2+) concentration ([Ca(2+)](i)) of differentiated podocytes was measured by single-cell fura-2 microfluorescence measurements. Free and total immunoreactive kinin levels were measured by radioimmunoassay.RESULTS: FSGS eluates increased the [Ca(2+)](i) levels concentration dependently (EC(50) 0.14 mg/ml; n = 3-19). 1 mg/ml eluate increased the [Ca(2+)](i) values reversibly from 82 +/- 12 to 1,462 +/- 370 nmol/l, and then they returned back to 100 +/- 16 nmol/l (n = 19). The eluate-induced increase of [Ca(2+)](i) consisted of an initial Ca(2+) peak followed by a Ca(2+) plateau which depended on the extracellular Ca(2+) concentration. The eluate-induced increase of [Ca(2+)](i) was inhibited by the specific B(2) kinin receptor antagonist Hoe 140 in a concentration-dependent manner (IC(50) 2.47 nmol/l). In addition, prior repetitive application of bradykinin desensitized the effect of eluate on [Ca(2+)](i). A colonic epithelial cell line not reacting to bradykinin did not respond to eluate either (n = 6). Similar to FSGS eluates, the eluate preparations of both the systemic lupus patient and the healthy volunteer led to a biphasic, concentration-dependent [Ca(2+)](i) increase in podocytes which again was inhibited by Hoe 140. Free kinins were detected in all eluate preparations.CONCLUSION: The procedure of antibody-based immunoadsorption leads to kinin in the eluate which elevates the [Ca(2+)](i) level of podocytes via B(2) kinin receptors.
AB - BACKGROUND/AIM: Patients with idiopathic focal segmental glomerulosclerosis (FSGS) often develop a recurrence of the disease after kidney transplantation. In a number of FSGS patients, plasmapheresis and immunoadsorption procedures have been shown to transiently reduce proteinuria and are thought to do this by eliminating a circulating factor. Direct cellular effects of eluates from immunoadsorption procedures on podocytes, the primary target of injury in FSGS, have not yet been reported.METHODS: Eluates were derived from antibody-based immunoadsorption of a patient suffering from primary FSGS, a patient with systemic lupus erythematosus, and a healthy volunteer. The cytosolic free Ca(2+) concentration ([Ca(2+)](i)) of differentiated podocytes was measured by single-cell fura-2 microfluorescence measurements. Free and total immunoreactive kinin levels were measured by radioimmunoassay.RESULTS: FSGS eluates increased the [Ca(2+)](i) levels concentration dependently (EC(50) 0.14 mg/ml; n = 3-19). 1 mg/ml eluate increased the [Ca(2+)](i) values reversibly from 82 +/- 12 to 1,462 +/- 370 nmol/l, and then they returned back to 100 +/- 16 nmol/l (n = 19). The eluate-induced increase of [Ca(2+)](i) consisted of an initial Ca(2+) peak followed by a Ca(2+) plateau which depended on the extracellular Ca(2+) concentration. The eluate-induced increase of [Ca(2+)](i) was inhibited by the specific B(2) kinin receptor antagonist Hoe 140 in a concentration-dependent manner (IC(50) 2.47 nmol/l). In addition, prior repetitive application of bradykinin desensitized the effect of eluate on [Ca(2+)](i). A colonic epithelial cell line not reacting to bradykinin did not respond to eluate either (n = 6). Similar to FSGS eluates, the eluate preparations of both the systemic lupus patient and the healthy volunteer led to a biphasic, concentration-dependent [Ca(2+)](i) increase in podocytes which again was inhibited by Hoe 140. Free kinins were detected in all eluate preparations.CONCLUSION: The procedure of antibody-based immunoadsorption leads to kinin in the eluate which elevates the [Ca(2+)](i) level of podocytes via B(2) kinin receptors.
KW - Bradykinin
KW - Calcium
KW - Cell Differentiation
KW - Cell Line
KW - Cytosol
KW - Female
KW - Glomerulosclerosis, Focal Segmental
KW - HT29 Cells
KW - Humans
KW - Immunosorbent Techniques
KW - Kidney Glomerulus
KW - Kidney Transplantation
KW - Kinins
KW - Lupus Nephritis
KW - Male
KW - Receptor, Bradykinin B2
KW - Receptors, Bradykinin
KW - Case Reports
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 68697
DO - 68697
M3 - SCORING: Journal article
C2 - 12590202
VL - 25
SP - 384
EP - 393
JO - KIDNEY BLOOD PRESS R
JF - KIDNEY BLOOD PRESS R
SN - 1420-4096
IS - 6
ER -