On the mechanisms of impaired phagocytosis in phosphate depletion.
Phosphate depletion (PD) impairs the phagocytic ability of polymorphonuclear leukocytes (PMNL). This derangement has been attributed to the low ATP content of PMNL in PD. The mechanisms responsible for the low ATP content are not well defined. Phosphorus deficiency, per se, and/or other cellular metabolic consequences of PD such as a rise in cytosolic calcium ([Ca2+]i) could be responsible. Indeed, PD is associated with a rise in [Ca2+]i in other cells, and such an event may inhibit mitochondrial ATP production. It is also not evident whether the impaired phagocytosis in PD is due to low ATP content and/or a rise in the [Ca2+]i of PMNL. The study presented here examined levels of [Ca2+]i, ATP content, and the phagocytic ability of PMNL from PD and pair-weighed (PW) rats and evaluated the potential beneficial effect of treatment with verapamil (V), which may prevent a rise in [Ca2+]i and the consequent effects on ATP content and the phagocytosis of PMNL. The resting levels of [Ca2+]i of PMNL from PD rats (148 +/- 3.9 nM) were significantly (P less than 0.01) higher, and the ATP contents (4.8 +/- 0.2 nmol/5 x 10(6) PMNL) were significantly (P less than 0.01) lower than in PW (111 +/- 2.8 nM and 9.3 +/- 0.3 nmol/5 x 10(6) PMNL), PW-V (114 +/- 2.2 nM and 9.3 +/- 0.28 nmol/5 x 10(6) PMNL), and PD-V (112 +/- 1.8 nM and 6.6 +/- 0.19 nmol/5 x 10(6) PMNL) animals. Despite the normal [Ca2+]i in the PMNL of PD-V rats, their ATP contents were still significantly (P less than 0.01) lower than those of PW or PW-V rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Kiersztejn
M
M
Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033.
Chervu
I
I
Smogorzewski
M
M
Fadda
G Z
GZ
Alexiewicz
J M
JM
Massry
S G
SG
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology*; D010710:Phosphates / Q000172:deficiency*; D051381:Rats; D011919:Rats, Inbred Strains
D010710:Phosphates; D000255:Adenosine Triphosphate; D002118:Calcium