| First Author | van Beek EM | Year | 2012 |
| Journal | Cell Rep | Volume | 2 |
| Issue | 4 | Pages | 748-55 |
| PubMed ID | 23022485 | Mgi Jnum | J:196223 |
| Mgi Id | MGI:5487487 | Doi | 10.1016/j.celrep.2012.08.027 |
| Citation | van Beek EM, et al. (2012) SIRPalpha controls the activity of the phagocyte NADPH oxidase by restricting the expression of gp91(phox). Cell Rep 2(4):748-55 |
| abstractText | The phagocyte NADPH oxidase mediates oxidative microbial killing in granulocytes and macrophages. However, because the reactive oxygen species produced by the NADPH oxidase can also be toxic to the host, it is essential to control its activity. Little is known about the endogenous mechanism(s) that limits NADPH oxidase activity. Here, we demonstrate that the myeloid-inhibitory receptor SIRPalpha acts as a negative regulator of the phagocyte NADPH oxidase. Phagocytes isolated from SIRPalpha mutant mice were shown to have an enhanced respiratory burst. Furthermore, overexpression of SIRPalpha in human myeloid cells prevented respiratory burst activation. The inhibitory effect required interactions between SIRPalpha and its natural ligand, CD47, as well as signaling through the SIRPalpha cytoplasmic immunoreceptor tyrosine-based inhibitory motifs. Suppression of the respiratory burst by SIRPalpha was caused by a selective repression of gp91(phox) expression, the catalytic component of the phagocyte NADPH oxidase complex. Thus, SIRPalpha can limit gp91(phox) expression during myeloid development, thereby controlling the magnitude of the respiratory burst in phagocytes. |
