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
| Autor: | Allen G. Harmsen, Maureen Howard, Simon Monard, Santiago Partida-Sanchez, Debra A. Cockayne, Stephen Goodrich, Elaine L. Jacobson, Troy D. Randall, Kim Kusser, Frances E. Lund, Norman J. Oppenheimer, Beth A. Garvy |
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| Rok vydání: | 2001 |
| Předmět: |
Lymphoid Tissue
Neutrophils Biology CD38 Cyclic ADP-ribose Cyclase Pneumococcal Infections General Biochemistry Genetics and Molecular Biology Calcium in biology Mice chemistry.chemical_compound NAD+ Nucleosidase Antigens CD Extracellular Animals Calcium Signaling ADP-ribosyl Cyclase Calcium signaling Mice Knockout Adenosine Diphosphate Ribose Cyclic ADP-Ribose Membrane Glycoproteins Ryanodine hemic and immune systems Chemotaxis General Medicine NAD ADP-ribosyl Cyclase 1 Antigens Differentiation Cell biology Mice Inbred C57BL N-Formylmethionine Leucyl-Phenylalanine Chemotaxis Leukocyte Streptococcus pneumoniae chemistry Second messenger system |
| Zdroj: | Nature Medicine. 7:1209-1216 |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm1101-1209 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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