TY - JOUR
T1 - A role for intracellular ph in membrane igm-mediated cell death of human B lymphomas
AU - Marches, R.
AU - Vitetta, E. S.
AU - Uhr, J. W.
PY - 2001/3/13
Y1 - 2001/3/13
N2 - We show that anti-lgM-induced cell death in a human B lymphoma cell line, B104, is associated with early intracellular acidification and cell shrinkage. In contrast, another human B cell lymphoma line, Daudi, less susceptible to B cell antigen receptor-mediated cell death, responded to anti-lgM with an early increase in intracellular pH (pHi). The anti-lgM-induced changes of phi were associated with different levels of activation of the Na+/H+ exchanger isoform 1 (NHE1) as judged by its phosphorylation status. Prevention of anti-lgM-induced cell death in B104 cells by the calcineurin phosphatase inhibitor, cyclosporin A, abrogated both intracellular acidification and cell shrinkage and was associated with an increase in the phosphorylation level of NHE1 within the first 60 min of stimulation. This indicates a key role for calcineurin in regulating phi and cell viability. The potential role of phi in cell viability was confirmed in Daudi cells treated with an Na+/H+ exchanger inhibitor 5-(N,N-hexamethylene)amiloride. These observations indicate that the outcome of the anti-lgM treatment depends on NHE1controlled pHi. We suggest that inactivation of the NHE1 in anti IgM-stimulated cells results in intracellular acidification and subsequently triggers or amplifies cell death.
AB - We show that anti-lgM-induced cell death in a human B lymphoma cell line, B104, is associated with early intracellular acidification and cell shrinkage. In contrast, another human B cell lymphoma line, Daudi, less susceptible to B cell antigen receptor-mediated cell death, responded to anti-lgM with an early increase in intracellular pH (pHi). The anti-lgM-induced changes of phi were associated with different levels of activation of the Na+/H+ exchanger isoform 1 (NHE1) as judged by its phosphorylation status. Prevention of anti-lgM-induced cell death in B104 cells by the calcineurin phosphatase inhibitor, cyclosporin A, abrogated both intracellular acidification and cell shrinkage and was associated with an increase in the phosphorylation level of NHE1 within the first 60 min of stimulation. This indicates a key role for calcineurin in regulating phi and cell viability. The potential role of phi in cell viability was confirmed in Daudi cells treated with an Na+/H+ exchanger inhibitor 5-(N,N-hexamethylene)amiloride. These observations indicate that the outcome of the anti-lgM treatment depends on NHE1controlled pHi. We suggest that inactivation of the NHE1 in anti IgM-stimulated cells results in intracellular acidification and subsequently triggers or amplifies cell death.
KW - B cell receptor
KW - Na/H exchanger
UR - http://www.scopus.com/inward/record.url?scp=0035853137&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035853137&partnerID=8YFLogxK
U2 - 10.1073/pnas.061028998
DO - 10.1073/pnas.061028998
M3 - Article
C2 - 11248096
AN - SCOPUS:0035853137
SN - 0027-8424
VL - 98
SP - 3434
EP - 3439
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 6
ER -