+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

Regulation of human neutrophil chemotaxis by intracellular pH

Journal of Biological Chemistry 261(14): 6492-6500
Regulation of human neutrophil chemotaxis by intracellular pH
The relationship of N-formyl-methionyl-leucyl-phenylalanine-stimulated Na+/H+ exchange to the chemotactic responsiveness of human neutrophils was investigated. The pHi changes, measured from the equilibrium distribution of 5,5-dimethyloxazolidine-2,4-dione, were correlated with the migratory behavior of the cells as assessed by the leading front method. Exposure of cells to 10 nM FMLP caused activation of Na+/H+ exchange, leading to a rise in pHi from approximately 7.25 to approximately 7.75. This intracellular alkalinization was inhibited by amiloride and by three more potent analogues. All four compounds reduced the chemotactic response to FMLP with apparent Ki values similar to those for inhibition of the pHi transients, thereby suggesting that the blocking effect of the drugs on directed cell migration was related to inhibition of Na+/H+ exchange. The effect was specific for stimulated cell locomotion: FMLP-induced chemotaxis and chemokinesis were inhibited in parallel, whereas random motility was unimpaired. The relationship of pHi to function was also studied as the pHi of FMLP-activated cells was varied between 6.8 and 8.6 by altering the chemical gradients for Na+ and H+ across the cell membrane. There was a direct, positive correlation between the pHi value attained following FMLP-stimulation and the locomotor response to a chemotactic gradient. These results indicate that the motile functions of human neutrophils can be regulated by their pHi.

Accession: 006288569

PMID: 3009458

Related references

Human neutrophil chemotaxis regulation by alpha-1 antitrypsin. 2011

EDRFS augment human neutrophil chemotaxis while inhibiting superoxide anion generation Role of intracellular S-nitrosothiol formation. Clinical Research 41(2): 224A, 1993

Inhibition of human neutrophil oxidative burst activity by entamoeba histolytica pore toxin is associated with altered neutrophil intracellular calcium and hydrogen regulation. Clinical Research 37(2): 422A, 1989

Nitric oxide and S-nitrosoglutathione augment human neutrophil chemotaxis while inhibiting superoxide anion generation Role of intracellular S-nitrosothiol formation. Arthritis & Rheumatism 36(9 SUPPL ): S243, 1993

Studies on the regulation of the neutrophil chemotactic response using a rapid and reliable method for measuring random migration and chemotaxis of neutrophil granulocytes. Agents and Actions 6(1-3): 326-339, 1976

Granulocyte colony-stimulating factor enhances neutrophil chemotaxis and attenuates alcohol-induced suppression of neutrophil chemotaxis in vitro. Alcoholism Clinical & Experimental Research 24(5 Supplement): 20A, May, 2000

Endothelial derived relaxation factor augments human neutrophil chemotaxis chemotaxis while inhibiting superoxide anion generation. Clinical Research 42(2): 255A, 1994

Evaluation of anti human neutrophil monoclonal antibodies effects of human neutrophil chemotaxis. Tissue Antigens 33(2): 215, 1989

A hierarchy of intracellular signalling determines neutrophil chemotaxis. FASEB Journal 16(5): A1211, March 22, 2002

Persistent neutrophil dysfunction in an adult. Combined defect in chemotaxis, phagocytosis and intracellular killing. American Journal of Medicine 57(2): 251-258, 1974