Abnormal cytoplasmic pH regulation during activation in uremic neutrophils.
Neutrophils isolated from ESRF patients demonstrated abnormal cytoplasmic pH changes after FMLP stimulation; the initial cytoplasmic acidification was absent (P less than 0.001 compared to controls) and the degree of alkalinization enhanced (P less than 0.05 compared to controls). This effect was not due to the absence of any of the factors associated with acidification in normal PMN since superoxide production was enhanced (P less than 0.05 compared to controls) and intracellular calcium release was normal. Our observations are not explicable by alterations in the function of the Na:H antiport since the kinetics of antiport activation by cytoplasmic pH were not different in uremic and control cells. Other factors must therefore be important in generating the abnormal pH response to chemotactic factors in uremic PMN. Cells from CAPD patients had some degree of initial acidification (P less than 0.001 compared to controls and P less than 0.05 compared to ESRF) and enhanced alkalinization (P less than 0.05 compared to controls). Preincubation of normal PMN in four-hour dwell PDE reproduced the responses of uremic PMN with absent acidification, enhanced alkalinization and enhanced superoxide generation after FMLP stimulation (P less than 0.05 compared to controls). Changes in the control of cytoplasmic pH in stimulated PMN may influence PMN function, and our observations may be relevant to the susceptibility of uremic patients to infection.
Haynes
A P
AP
Department of Haematology, City Hospital, Nottingham, England, United Kingdom.
Daniels
I
I
Porter
C
C
Fletcher
J
J
Morgan
A G
AG
D000328:Adult; D000368:Aged; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D010531:Peritoneal Dialysis, Continuous Ambulatory; D017923:Sodium-Hydrogen Exchangers; D013481:Superoxides / Q000378:metabolism; D014511:Uremia / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium