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- Title
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.
- Authors
Partida-Sanchez, Santiago; Cockayne, Debra A.; Monard, Simon; Jacobson, Elaine L.; Oppenheimer, Norman; Garvy, Beth; Kusser, Kim; Goodrich, Stephen; Howard, Maureen; Harmsen, Allen; Randall, Troy D.; Lund, Frances E.
- 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.
- Subjects
NEUTROPHILS; BACTERIAL diseases; AMINO acids; ADENOSINE diphosphate; CD antigens; CALCIUM channels; CELL migration; IMMUNE response; CHEMOTAXIS
- Publication
Nature Medicine, 2001, Vol 7, Issue 11, p1209
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm1101-1209