Na+/H+ exchange activation mediates the lipopolysaccharide-induced proliferation of human B lymphocytes and is impaired in malignant B-chronic lymphocytic leukemia lymphocytes

G. Gaidano, D. Ghigo, M. Schena, L. Bergui, S. Treves, F. Turrini, F. C. Cappio, A. Bosia

Research output: Contribution to journalArticle

Abstract

In various mammalian cell types the stimulation of the plasma membrane amiloride-sensitive Na+/H+ exchange and the resulting increase of intracellular pH (pH(i)) play a key role in the initiation of cell proliferation. In the present work we have investigated whether Na+/H+ exchange is involved in normal human B cell proliferation and whether it is also operating in malignant B-chronic lymphocytic leukemia (B-CLL) lymphocytes. Our results show that: 1) normal human B cells contain an operating Na+/H+ exchanger, as inferred by their ability to recover pH(i) after acid-loading in a HCO3 --free medium and by evidences that LPS and phorbol ester PMA elicit a pH(i) rise inhibitable by either 5-(N-ethyl-N-isopropyl)amiloride (EIPA) or a Na+-free medium; 2) LPS-induced proliferation of normal human B cells is strongly inhibited when the amiloride analog EIPA (5 μM) is present in the culture medium (after 72 h the proportion of B cells incorporation bromodeoxyuridine falls from 13.9 ± 3.9% to 2.8 ± 1.1%); 3) EIPA does not affect BdR incorporation when B cells proliferation is induced by the co-mitogenic activity of IL-4 and low m.w. B cell growth factor (BCGF); 4) B-CLL cells, which proliferate in response to IL-4/BCGF but not to LPS, fail to increase pH(i) above their pH(i) resting levels when challenged with LPS or PMA and pH(i) recovery after acid-loading is highly impaired. These results lead to conclude that Na+/H+ exchange operation is necessary for LPS-(but not for Il-4/BCGF)-induced proliferation of human normal B lymphocytes and that Na+/H+ exchange activation is impaired in malignant B-CLL lymphocytes.

Original languageEnglish
Pages (from-to)913-918
Number of pages6
JournalJournal of Immunology
Volume142
Issue number3
Publication statusPublished - 1989

Fingerprint

B-Cell Chronic Lymphocytic Leukemia
Lipopolysaccharides
B-Lymphocytes
Lymphocytes
Amiloride
Intercellular Signaling Peptides and Proteins
Cell Proliferation
Interleukin-4
Sodium-Hydrogen Antiporter
Acids
Phorbol Esters
Bromodeoxyuridine
Culture Media
Cell Membrane

ASJC Scopus subject areas

  • Immunology

Cite this

Na+/H+ exchange activation mediates the lipopolysaccharide-induced proliferation of human B lymphocytes and is impaired in malignant B-chronic lymphocytic leukemia lymphocytes. / Gaidano, G.; Ghigo, D.; Schena, M.; Bergui, L.; Treves, S.; Turrini, F.; Cappio, F. C.; Bosia, A.

In: Journal of Immunology, Vol. 142, No. 3, 1989, p. 913-918.

Research output: Contribution to journalArticle

Gaidano, G. ; Ghigo, D. ; Schena, M. ; Bergui, L. ; Treves, S. ; Turrini, F. ; Cappio, F. C. ; Bosia, A. / Na+/H+ exchange activation mediates the lipopolysaccharide-induced proliferation of human B lymphocytes and is impaired in malignant B-chronic lymphocytic leukemia lymphocytes. In: Journal of Immunology. 1989 ; Vol. 142, No. 3. pp. 913-918.
@article{64720f32c9cf40688ff812949cb1107b,
title = "Na+/H+ exchange activation mediates the lipopolysaccharide-induced proliferation of human B lymphocytes and is impaired in malignant B-chronic lymphocytic leukemia lymphocytes",
abstract = "In various mammalian cell types the stimulation of the plasma membrane amiloride-sensitive Na+/H+ exchange and the resulting increase of intracellular pH (pH(i)) play a key role in the initiation of cell proliferation. In the present work we have investigated whether Na+/H+ exchange is involved in normal human B cell proliferation and whether it is also operating in malignant B-chronic lymphocytic leukemia (B-CLL) lymphocytes. Our results show that: 1) normal human B cells contain an operating Na+/H+ exchanger, as inferred by their ability to recover pH(i) after acid-loading in a HCO3 --free medium and by evidences that LPS and phorbol ester PMA elicit a pH(i) rise inhibitable by either 5-(N-ethyl-N-isopropyl)amiloride (EIPA) or a Na+-free medium; 2) LPS-induced proliferation of normal human B cells is strongly inhibited when the amiloride analog EIPA (5 μM) is present in the culture medium (after 72 h the proportion of B cells incorporation bromodeoxyuridine falls from 13.9 ± 3.9{\%} to 2.8 ± 1.1{\%}); 3) EIPA does not affect BdR incorporation when B cells proliferation is induced by the co-mitogenic activity of IL-4 and low m.w. B cell growth factor (BCGF); 4) B-CLL cells, which proliferate in response to IL-4/BCGF but not to LPS, fail to increase pH(i) above their pH(i) resting levels when challenged with LPS or PMA and pH(i) recovery after acid-loading is highly impaired. These results lead to conclude that Na+/H+ exchange operation is necessary for LPS-(but not for Il-4/BCGF)-induced proliferation of human normal B lymphocytes and that Na+/H+ exchange activation is impaired in malignant B-CLL lymphocytes.",
author = "G. Gaidano and D. Ghigo and M. Schena and L. Bergui and S. Treves and F. Turrini and Cappio, {F. C.} and A. Bosia",
year = "1989",
language = "English",
volume = "142",
pages = "913--918",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - Na+/H+ exchange activation mediates the lipopolysaccharide-induced proliferation of human B lymphocytes and is impaired in malignant B-chronic lymphocytic leukemia lymphocytes

AU - Gaidano, G.

AU - Ghigo, D.

AU - Schena, M.

AU - Bergui, L.

AU - Treves, S.

AU - Turrini, F.

AU - Cappio, F. C.

AU - Bosia, A.

PY - 1989

Y1 - 1989

N2 - In various mammalian cell types the stimulation of the plasma membrane amiloride-sensitive Na+/H+ exchange and the resulting increase of intracellular pH (pH(i)) play a key role in the initiation of cell proliferation. In the present work we have investigated whether Na+/H+ exchange is involved in normal human B cell proliferation and whether it is also operating in malignant B-chronic lymphocytic leukemia (B-CLL) lymphocytes. Our results show that: 1) normal human B cells contain an operating Na+/H+ exchanger, as inferred by their ability to recover pH(i) after acid-loading in a HCO3 --free medium and by evidences that LPS and phorbol ester PMA elicit a pH(i) rise inhibitable by either 5-(N-ethyl-N-isopropyl)amiloride (EIPA) or a Na+-free medium; 2) LPS-induced proliferation of normal human B cells is strongly inhibited when the amiloride analog EIPA (5 μM) is present in the culture medium (after 72 h the proportion of B cells incorporation bromodeoxyuridine falls from 13.9 ± 3.9% to 2.8 ± 1.1%); 3) EIPA does not affect BdR incorporation when B cells proliferation is induced by the co-mitogenic activity of IL-4 and low m.w. B cell growth factor (BCGF); 4) B-CLL cells, which proliferate in response to IL-4/BCGF but not to LPS, fail to increase pH(i) above their pH(i) resting levels when challenged with LPS or PMA and pH(i) recovery after acid-loading is highly impaired. These results lead to conclude that Na+/H+ exchange operation is necessary for LPS-(but not for Il-4/BCGF)-induced proliferation of human normal B lymphocytes and that Na+/H+ exchange activation is impaired in malignant B-CLL lymphocytes.

AB - In various mammalian cell types the stimulation of the plasma membrane amiloride-sensitive Na+/H+ exchange and the resulting increase of intracellular pH (pH(i)) play a key role in the initiation of cell proliferation. In the present work we have investigated whether Na+/H+ exchange is involved in normal human B cell proliferation and whether it is also operating in malignant B-chronic lymphocytic leukemia (B-CLL) lymphocytes. Our results show that: 1) normal human B cells contain an operating Na+/H+ exchanger, as inferred by their ability to recover pH(i) after acid-loading in a HCO3 --free medium and by evidences that LPS and phorbol ester PMA elicit a pH(i) rise inhibitable by either 5-(N-ethyl-N-isopropyl)amiloride (EIPA) or a Na+-free medium; 2) LPS-induced proliferation of normal human B cells is strongly inhibited when the amiloride analog EIPA (5 μM) is present in the culture medium (after 72 h the proportion of B cells incorporation bromodeoxyuridine falls from 13.9 ± 3.9% to 2.8 ± 1.1%); 3) EIPA does not affect BdR incorporation when B cells proliferation is induced by the co-mitogenic activity of IL-4 and low m.w. B cell growth factor (BCGF); 4) B-CLL cells, which proliferate in response to IL-4/BCGF but not to LPS, fail to increase pH(i) above their pH(i) resting levels when challenged with LPS or PMA and pH(i) recovery after acid-loading is highly impaired. These results lead to conclude that Na+/H+ exchange operation is necessary for LPS-(but not for Il-4/BCGF)-induced proliferation of human normal B lymphocytes and that Na+/H+ exchange activation is impaired in malignant B-CLL lymphocytes.

UR - http://www.scopus.com/inward/record.url?scp=0024547856&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024547856&partnerID=8YFLogxK

M3 - Article

C2 - 2536415

AN - SCOPUS:0024547856

VL - 142

SP - 913

EP - 918

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -