β-NAD+e (extracellular β-NAD+), present at nanomolar levels in human plasma, has been implicated in the regulation of [Ca2+]i (the intracellular calcium concentration) in various cell types, including blood cells, by means of different mechanisms. Here, we demonstrate that micromolar NAD+e (both the α and the β extracellular NAD+ forms) induces a sustained [Ca2+]i increase in human granulocytes by triggering the following cascade of causally related events: (i) activation of adenylate cyclase and overproduction of cAMP; (ii) activation of protein kinase A; (iii) stimulation of ADP-ribosyl cyclase activity and consequent overproduction of cADP-ribose, a universal Ca2+ mobilizer; and (iv) influx of extracellular Ca2+. The NAD+e-triggered [Ca2+]i elevation translates into granulocyte activation, i.e. superoxide and nitric oxide generation, and enhanced chemotaxis in response to 0.1–10 μM NAD+e. Thus extracellular β-NAD+e behaves as a novel pro-inflammatory cytokine, stimulating human granulocytes and potentially recruiting them at sites of inflammation.
Skip Nav Destination
Follow us on Twitter @Biochem_Journal
Article navigation
February 2006
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
January 13 2006
Extracellular NAD+ regulates intracellular calcium levels and induces activation of human granulocytes
Santina Bruzzone;
Santina Bruzzone
*Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV/1, 16132 Genova, Italy
Search for other works by this author on:
Iliana Moreschi;
Iliana Moreschi
*Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV/1, 16132 Genova, Italy
Search for other works by this author on:
Lucrezia Guida;
Lucrezia Guida
*Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV/1, 16132 Genova, Italy
Search for other works by this author on:
Cesare Usai;
Cesare Usai
†Institute of Biophysics, CNR, Via De Marini 6, 16149 Genova, Italy
Search for other works by this author on:
Elena Zocchi;
Elena Zocchi
*Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV/1, 16132 Genova, Italy
Search for other works by this author on:
Antonio De Flora
Antonio De Flora
1
*Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV/1, 16132 Genova, Italy
1To whom correspondence should be addressed (email [email protected]).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
August 09 2005
Revision Received:
October 05 2005
Accepted:
October 14 2005
Accepted Manuscript online:
October 14 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2006
Biochem J (2006) 393 (3): 697–704.
Article history
Received:
August 09 2005
Revision Received:
October 05 2005
Accepted:
October 14 2005
Accepted Manuscript online:
October 14 2005
Citation
Santina Bruzzone, Iliana Moreschi, Lucrezia Guida, Cesare Usai, Elena Zocchi, Antonio De Flora; Extracellular NAD+ regulates intracellular calcium levels and induces activation of human granulocytes. Biochem J 1 February 2006; 393 (3): 697–704. doi: https://doi.org/10.1042/BJ20051302
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Follow us on Twitter @Biochem_Journal
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() View past webinars > |