Stimulation of the Na+/H+ exchanger in human endothelial cells activated by granulocyte- and granulocyte-macrophage-colony-stimulating factor. Evidence for a role in proliferation and migration.
It has been shown that human endothelial cells (HEC) are stimulated to migrate and proliferate by granulocyte (G)- and granulocyte-macrophage (GM)-colony-stimulating factor (CSF) (Bussolino, F., Wang, J. M., Defilipii, P. Turrini, F., Sanavio, F., Edgell, C.-J. S., Aglietta, M., Arese, P., and Mantovani, A. (1989) Nature 337, 471-473). The rapid intracellular events initiated by these cytokines on binding to their receptors on HEC are not defined. Addition of G- or GM-CSF to HEC produced a rapid activation of Na+/H+ exchanger resulting in an increase in intracellular pH (pHi). Both cytokines induced an alkaline displacement in the pHi dependence of the exchanger without affecting the affinity for external Na+ (Nao) and the rate of exchanger. Ethylisopropylamiloride, a selective inhibitor of the Na+/H+ exchanger, inhibited the intracellular alkalinization, the migration, and proliferation induced by G- and GM-CSF. The data indicate that G- and GM-CSF initiate a rapid exchange of Na+ and H+ by means of the Na+/H+ exchanger and that this ethylisopropylamiloride-sensitive ions flux is important to the biological effects of these cytokines on HEC.
Bussolino
F
F
Dipartimento di Genetica, Universita di Torino, Italy.
Wang
J M
JM
Turrini
F
F
Alessi
D
D
Ghigo
D
D
Costamagna
C
C
Pescarmona
G
G
Mantovani
A
A
Bosia
A
A
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D012964:Sodium / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers; D014471:Umbilical Veins
D002352:Carrier Proteins; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D017923:Sodium-Hydrogen Exchangers; D016179:Granulocyte Colony-Stimulating Factor; D000584:Amiloride; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D012964:Sodium; C039614:ethylisopropylamiloride