| First Author | Pan YF | Year | 2013 |
| Journal | Eur J Immunol | Volume | 43 |
| Issue | 6 | Pages | 1598-607 |
| PubMed ID | 23504624 | Mgi Jnum | J:198122 |
| Mgi Id | MGI:5495566 | Doi | 10.1002/eji.201243031 |
| Citation | Pan YF, et al. (2013) Signal regulatory protein alpha negatively regulates mast-cell activation following FcepsilonRI aggregation. Eur J Immunol 43(6):1598-607 |
| abstractText | Mast cells elicit allergic reaction through degranulation and release of proinflammatory mediators after aggregation of the IgE receptor FcepsilonRI. Here we provide evidence to show that signal regulatory protein alpha (SIRPalpha), an ITIM-containing receptor, is an endogenous regulator of IgE-Ag induced mast-cell activation. SIRPalpha expression is promptly reduced in mast cells in response to FcepsilonRI aggregation. Impaired expression of SIRPalpha in mast cells facilitates FcepsilonRI-evoked degranulation and de novo synthesis of cytokines (IL-4, IL-13, IL-6, and TNF-alpha). We further demonstrate that SIRPalpha knockdown in mast cells accelerates calcium mobilization and affects cytoskeletal rearrangement (F-actin disassembly and polymeric tubulin formation) after FcepsilonRI aggregation. Mechanistic studies highlight the prolonged activation of NF-kappaB and MAPKs as well as PLC-gamma after FcepsilonRI stimulation as a consequence of the inhibition of SIRPalpha expression in mast cells. Immunoprecipitation analysis shows that SIRPalpha knockdown markedly increases IgE-induced SHP2 interaction with PI3K regulatory subunit PI3Kp85 or IKK-beta in mast cells, indicating that SIRPalpha may accomplish this through its association and sequestration of SHP2. Collectively, our results strongly indicate that SIRPalpha is a biological important regulator of FcepsilonRI signaling. |
