Deficient phospholipase C activity in blood polimorphonuclear neutrophils from patients with liver cirrhosis.
OBJECTIVE
Circulating neutrophils from cirrhotic patients have a reduced capacity to generate superoxide anion (O(2)(-)), which might contribute to frequent bacterial infections in these patients. We studied the signal transduction pathways involved in the generation of O(2)(-) in neutrophils from 98 cirrhotic patients and 46 healthy controls.


METHODS
We measured O(2)(-) production in neutrophils induced by fMLP, opsonized zymosan, TNF alpha, NaF, AlF(4)(-), A23187 and phorbol myristate acetate. Furthermore, we measured phospholipase C activity in neutrophils from healthy controls and end-stage cirrhotic patients.


RESULTS
O(2)(-) production was decreased in neutrophils from patients in response to fMLP, opsonized zymosan and TNF alpha. Likewise, response of these cells to G-protein stimulation by fluorides was also decreased. These reduced responses correlated significantly with the degree of liver dysfunction. On the contrary, neutrophils from patients responded normally to A23187 and phorbol esters stimulation indicating that Ca(2+)- and PKC-dependent pathways are intact in these cells. Finally, phospholipase C activity was markedly reduced in neutrophils from end-stage liver cirrhosis.


CONCLUSIONS
These data confirm that O(2)(-) generation by neutrophils is decreased in patients with cirrhosis, particularly in those with more severe liver dysfunction, and suggest that this defect involves phosphatidylinositol specific phospholipase C activity.
Garfia
Cristina
C
Gastroenterology Department and Research Center, Servicio de Aparato Digestivo, Hospital Universitario, 12 de Octubre, Universidad Complutense, Carretera de Andalucía, Km 5.400, Madrid 28041, Spain.
García-Ruiz
Inmaculada
I
Solís-Herruzo
José Antonio
JA
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005459:Fluorides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D008103:Liver Cirrhosis / Q000097:blood / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019255:NADPH Oxidases / Q000097:blood; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D009195:Peroxidase / Q000097:blood; D015398:Signal Transduction; D013481:Superoxides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D010738:Type C Phospholipases / Q000097:blood / Q000172:deficiency*; D015054:Zymosan / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; D009195:Peroxidase; D019255:NADPH Oxidases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D005459:Fluorides