title: Effects of hypertonic saline on expression of human polymorphonuclear leukocyte adhesion molecules.
abstract: Hypertonic saline prevents vascular adherence of neutrophils and ameliorates ischemic tissue injury. We hypothesized that hypertonic saline attenuates N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated expression of adhesion molecules on human polymorphonuclear leukocytes (PMNLs). fMLP-stimulated up-regulation of beta2-integrins was diminished by hypertonic saline but not by hypertonic choline chloride-, mannitol-, or sucrose-modified Hanks' buffered salt solution. Shedding of L-selectin was decreased by hypertonic saline and choline chloride but not by hypertonic mannitol or sucrose. When the effects of hypertonic sodium chloride- and choline chloride-modified media were compared, neither solution affected fMLP-receptor binding but both equally inhibited fMLP-stimulated increase in intracellular calcium, ionophore A23187, and phorbol myristate acetate (PMA)-stimulated numerical up-regulation of beta2-integrins. Analysis of mitogen-activated protein (MAP) kinases p38 and p44/42 for phosphorylation revealed that hypertonic solutions did not differ in preventing fMLP-stimulated increases in phospho-p38 and phospho-p44/42. Resting PMNLs shrunk by hypertonic saline increased their volume during incubation and further during chemotactic stimulation. Addition of amiloride further enhanced inhibition of up-regulation of beta2-integrins. No fMLP-stimulated volume changes occurred in PMNLs exposed to hypertonic choline chloride, resulting in significant cell shrinkage. Results suggest a sodium-specific inhibitory effect on up-regulation of beta2-integrins of fMLP-stimulated PMNLs, which is unlikely to be caused by alterations of fMLP receptor binding, decrease in cytosolic calcium, attenuation of calcium or protein kinase C-dependent pathways, suppression of p38- or p44/42 MAP kinase-dependent pathways, or cellular ability to increase or decrease volumes.
authors.affiliation: Department of Anesthesiology and the. Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany. manfried.thiel@ana.med.uni-muenchen.de
authors.forename: M
authors.initials: M
authors.lastname: Thiel
authors.forename: F
authors.initials: F
authors.lastname: Buessecker
authors.forename: K
authors.initials: K
authors.lastname: Eberhardt
authors.forename: A
authors.initials: A
authors.lastname: Chouker
authors.forename: F
authors.initials: F
authors.lastname: Setzer
authors.forename: U
authors.initials: U
authors.lastname: Kreimeier
authors.forename: K E
authors.initials: KE
authors.lastname: Arfors
authors.forename: K
authors.initials: K
authors.lastname: Peter
authors.forename: K
authors.initials: K
authors.lastname: Messmer
mesh_terms: D018821:CD18 Antigens / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000187:drug effects; D006801:Humans; D019041:L-Selectin / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000737:chemistry*; D010766:Phosphorylation / Q000187:drug effects; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D012462:Saline Solution, Hypertonic; D019041:L-Selectin; D012965:Sodium Chloride; D009240:N-Formylmethionine Leucyl-Phenylalanine; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium