SLP-76 deficiency impairs signaling via the high-affinity IgE receptor in mast cells

SLP-76 is an adapter protein expressed in T cells and myeloid. cells that i s a substrate for ZAP-70 and Syk. SLP-76-deficient mice exhibit a profound block in T-cell development. We found that although SLP-76 is expressed in mouse mast cells, SLP-76(-/-) mice have normal numbers of mast cells in the ir skin and bronchi. SLP-76(-/-) mice are resistant to IgE-mediated passive anaphylaxis. SLP-76(-)/(-) mice sensitized with IgE anti-dinitrophenyl (DN P) and then challenged with DNP-HSA developed only mild and transient tachy cardia, failed to increase their plasma histamine level, and all survived t he antigen challenge. Bone marrow-derived mast cells (BMMCs) from SLP76(-/- ) mice failed to release beta-hexosaminidase and to secrete IL-6 after Fc e psilon RI cross-linking. Tyrosine phosphorylation of phospholipase C-gamma 1 (but not of Syk) and calcium mobilization in response to IgE cross-linkin g were reduced in SLP-76-deficient BMMCs. These results suggest that SLP-76 plays an important role in Fc epsilon RI-mediated signaling in mast cells.