Lyn but not Fyn kinase controls IgG-mediated systemic anaphylaxis.

Journal Article (Journal Article)

Anaphylaxis is a rapid, life-threatening hypersensitivity reaction. Until recently, it was mainly attributed to histamine released by mast cells activated by allergen crosslinking (XL) of FcεRI-bound allergen-specific IgE. However, recent reports established that anaphylaxis could also be triggered by basophil, macrophage, and neutrophil secretion of platelet-activating factor subsequent to FcγR stimulation by IgG/Ag complexes. We have investigated the contribution of Fyn and Lyn tyrosine kinases to FcγRIIb and FcγRIII signaling in the context of IgG-mediated passive systemic anaphylaxis (PSA). We found that mast cell IgG XL induced Fyn, Lyn, Akt, Erk, p38, and JNK phosphorylation. Additionally, IgG XL of mast cells, basophils, and macrophages resulted in Fyn- and Lyn-regulated mediator release in vitro. FcγR-mediated activation was enhanced in Lyn-deficient (knockout [KO]) cells, but decreased in Fyn KO cells, compared with wild-type cells. More importantly, Lyn KO mice displayed significantly exacerbated PSA features whereas no change was observed for Fyn KO mice, compared with wild-type littermates. Intriguingly, we establish that mast cells account for most serum histamine in IgG-induced PSA. Taken together, our findings establish pivotal roles for Fyn and Lyn in the regulation of PSA and highlight their unsuspected functions in IgG-mediated pathologies.

Full Text

Duke Authors

Cited Authors

  • Falanga, YT; Chaimowitz, NS; Charles, N; Finkelman, FD; Pullen, NA; Barbour, S; Dholaria, K; Faber, T; Kolawole, M; Huang, B; Odom, S; Rivera, J; Carlyon, J; Conrad, DH; Spiegel, S; Oskeritzian, CA; Ryan, JJ

Published Date

  • May 1, 2012

Published In

Volume / Issue

  • 188 / 9

Start / End Page

  • 4360 - 4368

PubMed ID

  • 22450804

Pubmed Central ID

  • PMC3536057

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1003223


  • eng

Conference Location

  • United States