Splenic B Lymphocyte Programmed Cell Death Is Prevented by Nitric Oxide Release Through Mechanisms Involving Sustained Bcl-2 Levels

ANA MARÍA GENARO; SONSOLES HORTELANO; A ALVAREZ; CARLOS MARTINEZ-A; LISARDO BOSCÁ

JOURNAL OF CLINICAL INVESTIGATION

AMER SOC CLINICAL INVESTIGATION INC

Lugar: Ann Arbor; Año: 1995 vol. 95 p. 1884 - 1890

0021-9738

Incubation of ex vivo cultured mature B cells in the presence of nitric oxide or nitric oxide-donor substances delays programmed cell death as determined by the appearance ofDNA laddering in agarose gel electrophoresis or by flowcytometry analysis of DNA. Nitric oxide also rescues B cells from antigen-induced apoptosis but fails to provide a costimulatory signal that converts the signal elicited by the antigen into a proliferative response. The protective effects of nitric oxide against programmed cell death can be reproduced by treatment of the cells with permeant analogues of cyclic GMP. Regarding the mechanisms by which nitric oxide prevents apoptosis in B cells, we have observed thatnitric oxide release prevents the drop in the expression of the protooncogene bcl-2, both at the mRNA and protein levels, suggesting the existence of an unknown pathway thatlinks nitric oxide signaling with Bcl-2 expression.