Deficient protein kinase C-dependent Na+/H+ exchanger activity in T cells from bone marrow transplantation recipients.
The early Na+/H+ exchanger-mediated alkalinization of intracellular pH (pHi) was analyzed in peripheral blood T cells from 23 bone marrow transplantation (BMT) recipients (17 allogeneic and 6 autologous) and a group of 13 healthy controls, in response to stimulation of protein kinase C (PKC) with a phorbol ester. In parallel we evaluated the proliferative response of peripheral blood T cells to an anti-CD3 mAb in the presence of either IL-2 or PMA. The pHi increase (delta pHi) observed in control samples ranged from 0.14 to 0.23 pH units (X +/- SD = 0.17 +/- 0.03). In 10 allogeneic and four autologous BMT recipients the delta pHi was under the lower limit of the control range (range: 0.01 to 0.09, X +/- SD = 0.05 +/- 0.02), whereas the remaining nine cases responded similarly to control samples (range: 0.14 to 0.24, X +/- SD = 0.17 +/- 0.04). The response of the Na+/H+ antiporter to a PKC-independent osmotic stimulation appeared to be normal, thus indicating that the intrinsic Na+/H+ exchanger activity was unaltered. The anti-CD3 induced proliferative response of the group of samples displaying a suboptimal delta pHi, was significantly lower (p less than 0.01) than that detected in control samples. T cell proliferation in samples from BMT recipients displaying a normal delta pHi was undistinguishable from the control group (p greater than 0.05). Our results provide the first evidence for a defective early metabolic event, closely related to PKC activity, in T cells from BMT recipients displaying a low proliferative response to T cell mitogens.
Izquierdo
M
M
Servicio de Inmunologia y Hematologia, Universidad Autónoma, Madrid, Spain.
Redondo
J M
JM
Balboa
M A
MA
López-Rivas
A
A
Cragoe
E J
EJ
Vázquez
L
L
Fernández-Rañada
J M
JM
López-Botet
M
M
D016026:Bone Marrow Transplantation; D002352:Carrier Proteins / Q000378:metabolism*; D006086:Graft vs Host Disease / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008213:Lymphocyte Activation; D010641:Phenotype; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000172:deficiency* / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers; D013601:T-Lymphocytes / Q000145:classification / Q000201:enzymology* / Q000378:metabolism; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C