Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium
Author: ["Santiago Partida-Sánchez","Debra A. Cockayne","Simon Monard","Elaine L. Jacobson","Norman Oppenheimer","Beth Garvy","Kim Kusser","Stephen Goodrich","Maureen Howard","Allen Harmsen","Troy D. Randall","Frances E. Lund"]
Publication: Nature Medicine
CITE.CC academic search helps you expand the influence of your papers.
Abstract
Cyclic ADP-ribose is believed to be an important calcium-mobilizing second messenger in invertebrate, mammalian and plant cells. CD38, the best-characterized mammalian ADP-ribosyl cyclase, is postulated to be an important source of cyclic ADP-ribose in vivo. Using CD38-deficient mice, we demonstrate that the loss of CD38 renders mice susceptible to bacterial infections due to an inability of CD38-deficient neutrophils to directionally migrate to the site of infection. Furthermore, we show that cyclic ADP-ribose can directly induce intracellular Ca++ release in neutrophils and is required for sustained extracellular Ca++ influx in neutrophils that have been stimulated by the bacterial chemoattractant, formyl-methionyl-leucyl-phenylalanine (fMLP). Finally, we demonstrate that neutrophil chemotaxis to fMLP is dependent on Ca++ mobilization mediated by cyclic ADP-ribose. Thus, CD38 controls neutrophil chemotaxis to bacterial chemoattractants through its production of cyclic ADP-ribose, and acts as a critical regulator of inflammation and innate immune responses.
Cite this article
Partida-Sánchez, S., Cockayne, D., Monard, S. et al. Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo. Nat Med 7, 1209–1216 (2001). https://doi.org/10.1038/nm1101-1209
