Inducible nitric oxide synthase is a major intermediate in signaling pathways for the survival of plasma cells.
While a number of extrinsic factors are known to promote the survival of plasma cells (PCs), the signaling intermediates involved remain poorly characterized. Here we identified inducible nitric oxide synthase (iNOS) as an intermediate that supported the survival of PCs. PCs deficient in iNOS (Nos2(-/-) PCs) showed enhanced death in vitro, after transfer into congenic adoptive hosts, and in chimeras made with wild-type and Nos2(-/-) bone marrow. The iNOS-mediated protection involved activation of protein kinase G and modulation of endoplasmic reticulum stress components. Activation of caspases was also diminished. We found that iNOS was required for PCs to respond to some prosurvival mediators associated with bone marrow stromal cells and that at least one mediator, interleukin 6, fed directly into this pathway by inducing iNOS.
1] National Institute of Immunology, New Delhi, India. [2].
Ankur S
AS
Saini
1] National Institute of Immunology, New Delhi, India. [2] [3].
Gautam N
GN
Shenoy
1] National Institute of Immunology, New Delhi, India. [2].
Satyajit
S
Rath
1] National Institute of Immunology, New Delhi, India. [2].
Vineeta
V
Bal
1] National Institute of Immunology, New Delhi, India. [2].
Anna
A
George
D019264:Adoptive Transfer; D000818:Animals; D002470:Cell Survival / Q000276:immunology; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000276:immunology* / Q000378:metabolism; D010950:Plasma Cells / Q000201:enzymology / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*
D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse