Inhibition of cytochalasin-primed neutrophils by hyperosmolarity.
Experimental and clinical investigations using hyperosmotic solutions for resuscitation of hemorrhagic shock demonstrated modulation of the inflammatory response. Decreased postinjury hyperinflammation has been attributed to a reduction in neutrophil-mediated tissue damage. This study shows that cytoskeletal disruption with cytochalasinB did not reverse or prevent the inhibitory effect of an osmolarity increase on the neutrophil cytotoxic response to a formyl peptide. In cytochalasin-primed neutrophils, the hyperosmolarity-dependent inhibition promptly reversed after returning to iso-osmotic levels. Paradoxically, an increase in osmolarity after stimulation produced an increase in the release of reactive oxygen species to the extracellular medium. The inhibitory effect of hyperosmotic NaCl can be reproduced by solutions of similar osmolarity containing N-methyl glucamine or sucrose, but solutions containing mannitol allowed an almost complete response to N-formyl methionyl leucyl phenylalanine. The effects on the release of reactive oxygen species to the extracellular media found with the OxyBURST-bovine serum albumin assay correlated with the changes of the intracellular calcium signal, indicating that the inhibition by hyperosmolarity occurs near the receptor level.
Giambelluca
Miriam S
MS
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, UNLP, La Plata, Argentina.
Gende
Oscar A
OA
D002118:Calcium / Q000378:metabolism; D002630:Chemotactic Factors / Q000378:metabolism; D003571:Cytochalasin B / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008954:Models, Biological; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D009994:Osmolar Concentration; D009995:Osmosis; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D012965:Sodium Chloride / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D002630:Chemotactic Factors; D017382:Reactive Oxygen Species; D013481:Superoxides; D003571:Cytochalasin B; D012965:Sodium Chloride; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium