Effect of amlodipine therapy on the monoclonal antibody 3G8-induced calcium signal in polymorphonuclear leukocytes of hemodialysis patients.
Chronic renal failure is associated with impaired phagocytosis. This was attributed to the PTH-induced elevation of basal levels of [Ca2+]i of polymorphonuclear leukocytes (PMNLs) and to the small calcium transient induced by the ligation of the Fcgamma RIII receptors of these cells with 3G8 monoclonal antibodies. The blocking of the action of PTH on the PMNLs of patients with chronic renal failure by their treatment with a calcium channel blocker normalized the basal levels of [Ca2+]i of the PMNLs and reversed the defect in their phagocytic property. It is not known whether such therapy would also restore the calcium transient in the PMNLs in response to 3G8 monoclonal antibody to normal. We examined this issue in 12 normal subjects and 18 hemodialysis patients; 9 of them were treated with the calcium channel blocker, amlodipine, and the other 9 did not receive such therapy. The treatment with amlodipine normalized [Ca2+]i of PMNLs as well as the calcium transient in response to 3G8 monoclonal antibody and reversed the defect in their phagocytosis. It is concluded that chronic renal failure is associated with deranged calcium homeostasis of PMNLs which causes abnormalities in the function of Fcgamma RIII receptors and consequently results in impaired phagocytosis. Therapy with a calcium channel blocker can reverse all these derangements in metabolism and function of PMNLs.
Ahmed
A
A
Division of Nephrology and Department of Medicine, University of Southern California School of Medicine, Los Angeles, CA 90033, USA.
Krol
E
E
Smogorzewski
M
M
Massry
S G
SG
D000328:Adult; D017311:Amlodipine / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D020013:Calcium Signaling / Q000187:drug effects*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis; D006435:Renal Dialysis
D000911:Antibodies, Monoclonal; D002121:Calcium Channel Blockers; D017311:Amlodipine