Effects of hypertonic saline on expression of human polymorphonuclear leukocyte adhesion molecules

Hypertonic saline prevents vascular adherence of neutrophils and ameliorate s ischemic tissue injury. We hypothesized that hypertonic saline attenuates N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated expression of ad hesion molecules on human polymorphonuclear leukocytes (PMNLs). fMLP-stimul ated up-regulation of beta2-integrins was diminished by hypertonic saline b ut not by hypertonic choline chloride-, mannitol-, or sucrose-modified Hank s' buffered salt solution. Shedding of L-selectin was decreased by hyperton ic saline and choline chloride but not by hypertonic mannitol or sucrose. W hen the effects of hypertonic sodium chloride- and choline chloride-modifie d media were compared, neither solution affected fMLP-receptor binding but both equally inhibited fMLP-stimulated increase in intracellular calcium, i onophore A23187, and phorbol myristate acetate (PMA)-stimulated numerical u p-regulation of beta2-integrins. Analysis of mitogen-activated protein (MAP ) kinases p38 and p44/42 for phosphorylation revealed that hypertonic solut ions did not differ in preventing fMLP-stimulated increases in phospho-p38 and phospho-p44/42. Resting PMNLs shrunk by hypertonic saline increased the ir volume during incubation and further during chemotactic stimulation. Add ition of amiloride further enhanced inhibition of up-regulation of beta2-in tegrins. No fMLP-stimulated volume changes occurred in PMNLs exposed to hyp ertonic choline chloride, resulting in significant cell shrinkage. Results suggest a sodium-specific inhibitory effect on up-regulation of beta2-integ rins of fMLP-stimulated PMNLs, which is unlikely to be caused by alteration s of fMLP receptor binding, decrease in cytosolic calcium, attenuation of c alcium or protein kinase C-dependent pathways, suppression of p38- or p44/4 2 MAP kinase-dependent pathways, or cellular ability to increase or decreas e volumes.