Mannitol Upregulates Monocyte HLA-DR, Monocyte and Neutrophil CD11b, and Inhibits Neutrophil Apoptosis
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Mannitol Upregulates Monocyte HLA-DR, Monocyte and Neutrophil CD11b, and Inhibits Neutrophil Apoptosis Matthias Turina,1,2,3,4 Aaron Mulhall,1,2 Sarah Gardner,1,2 Hiram C. Polk Jr.,1,2 and Frederick N. Miller3
Abstract—D-Mannitol is a substance widely used for both clinical applications as a strong diuretic and in basic research as a purportedly inert osmotic control substance. However, recent experiments have shown that mannitol is able to decrease neutrophil apoptosis in vitro by more than 25%. The aim of the current study was to assess mannitol_s effects on two immune cell activation markers; CD11b on neutrophils and monocytes, and HLA-DR on monocytes. Exposure of diluted whole blood (1:10 in RPMI 1640) to increasing concentrations of mannitol for 24 h was associated with a significant increase in both monocyte and neutrophil CD11b expression in non-lipopolysaccharide (LPS)-stimulated samples. Monocyte HLA-DR, but not neutrophil HLA-DR, was significantly higher in the presence of 16.5 mM/l mannitol, whereas isoosmolar NaCl had no effect. Levels of IL-6 and TNF-a were not affected by mannitol in our model. All reagents were tested negative for endotoxin contamination. Together, these data indicate that mannitol may directly interact with neutrophils and monocytes. Further systematic evaluation is indicated to define the precise immunomodulating actions of mannitol, and to assess these effects in patients receiving such therapy. KEY WORDS: mannitol; neutrophil; monocyte; CD11b; HLA-DR; apoptosis.
found in human urine [1]. Following intravenous injection, mannitol almost completely remains in the intravascular compartment, is metabolized at a very slow rate in the liver by direct oxidation [2], and is almost entirely excreted by renal filtration without tubular reabsorption. Ever since Smith et al. in the 1940s showed that mannitol clearance closely reflected glomerular filtration rate in man [3], there has been clinical interest in the therapeutic use of mannitol. Its ability to increase vascular osmolarity without being metabolized or having significant toxic effects make it a strong yet safe osmotic diuretic. Its main clinical applications today are in the therapy of severe nephritic syndrome, cirrhosis with ascites or congestive heart failure, as an osmotic agent to replace dextrose in peritoneal dialysis solutions, or to reduce intracranial pressure following traumatic brain injury, neurosurgery, or other conditions leading to cerebral edema [4].
INTRODUCTION D-Mannitol, C6H14O6, is a commercially available hexose with a molecular weight of 182 g/mol. Its structure closely resembles that of dextrose, from which it is artificially prepared by a simple chemical reduction process. D-mannitol, but not its enantiomer L-mannitol, exists naturally in many plants, algae, fungi, and certain bacteria, whereas only traces of it are occasionally 1
Department of Surgery, Price Institute of Surgical Research, University of Louisville School of Medicine, Louisville, KY, USA. 2 Trauma Program in Surgery, University of Lou
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