Impaired phagocytosis in chronic renal failure is mediated by secondary hyperparathyroidism.
Patients with chronic renal failure (CRF) display impaired phagocytosis by the polymorphonuclear leucocytes (PMNL), and these cells have elevated basal levels of cytosolic calcium ([Ca2+]i) and reduced ATP content. It has been suggested that these changes in PMNL metabolism and function are mediated by the state of secondary hyperparathyroidism of CRF. To examine the role of excess PTH in these derangements of PMNL, we studied [Ca2+]i, ATP and phagocytic ability of PMNL in five groups of rats including: CRF, CRF normocalcemic parathyroidectomized (CRF-PTX), CRF and normal animals treated with verapamil (CRF-V), and normal-V, respectively. The level of [Ca2+]i in the PMNL of CRF rats (149 +/- 2.7 nM) was significantly (P less than 0.01) higher and the ATP content (4.2 +/- 0.17 nmol/5 x 10(6) PMNL) significantly lower (P less than 0.01) than in normal (108 +/- 2.4 nM; 9.5 +/- 0.15 nmol/5 x 10(6) PMNL), CRF-PTX (103 +/- 2.9 nM; 9.2 +/- 0.19 nmol/5 x 10(6) PMNL), CRF-V (107 +/- 2.2 nM; 9.0 +/- 0.2 nmol/5 x 10(6) PMNL) and normal-V (106 +/- 1.8 nM; 9.2 +/- 0.2 nmol/5 x 10(6) PMNL), despite sustained elevation in blood PTH in the CRF-V group. Phagocytosis was significantly (P less than 0.01) impaired in CRF animals (5.6 +/- 0.25 micrograms oil/10(7) PMNL/min) but was normal in CRF-PTX (9.3 +/- 0.21 micrograms oil/10(7) PMNL/min) and CRF-V (9.5 +/- 0.22 micrograms oil/10(7) PMNL/min) rats. The values of phagocytosis in normal and normal-V rats were 9.6 +/- 44 and 9.6 +/- 0.18 micrograms oil/10(7) PMNL/min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Chervu
I
I
Department of Medicine, University of Southern California School of Medicine, Los Angeles.
Kiersztejn
M
M
Alexiewicz
J M
JM
Fadda
G Z
GZ
Smogorzewski
M
M
Massry
S G
SG
D000818:Animals; D002118:Calcium / Q000097:blood; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000503:physiopathology*; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010281:Parathyroid Hormone / Q000097:blood; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D010758:Phosphorus / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D010281:Parathyroid Hormone; D010758:Phosphorus; D014700:Verapamil; D002118:Calcium