NEUTROPHIL FUNCTION IN HYPEROSMOTIC NACL IS PRESERVED BY PHOSPHOENOL PYRUVATE

Hyperosmolarity in the urinary tract inhibits the host defense against bacterial infection. NaCl contributes most to osmolarity in the renal medulla and urine. Therefore, we studied the effect of hyperosmolar NaCl on neutrophil function. When osmolarity was increased by NaCl, polymorphonuclear leukocytes (PMNL) became defective in phagocytosis, intracellular killing of bacteria, chemotactic activity, and superoxide production. This coincided with a decrease in the intracellular adenosine triphosphate (ATP) content of PMNL. Both the inhibition of superoxide production and the reduction in ATP content did not occur at 4-degrees-C. By increasing ATP content, phosphoenol pyruvic acid (PEP) protected against the decrease in superoxide production. These results suggest that leukocyte function is inhibited by high concentrations of NaCl due to the activation of the Na+-K+ pump. PEP, an ATP precursor, can protect PMNL against osmotic stress by raising the intracellular concentration of ATP.