SLP-76 regulates Fcγ receptor and integrin signaling in neutrophils

Sally A. Newbrough, Attila Mocsai, Regina A. Clemens, Jennifer N. Wu, Michael A. Silverman, Andrew L. Singer, Clifford A. Lowell, Gary A. Koretzky

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

While the contribution of intracellular adaptor proteins to lymphocyte activation has been well studied, the function of these molecules in innate immune effector cells such as neutrophils has not been extensively addressed. Here we demonstrate a critical role for the adaptor molecule SH2 domain-containing leukoctye-specific phosphoprotein of 76 kDa (SLP-76) in FcγR and integrin signaling. Stimulation of these receptors induces tyrosine phosphorylation and cytoplasmic relocalization of SLP-76 in freshly isolated murine neutrophils. Neutrophils lacking SLP-76 demonstrate decreased FcγR-induced calcium flux and reactive oxygen intermediate (ROI) production in response to immune complex stimulation. More dramatically, SLP-76-/- neutrophils fail to produce ROI, spread, or activate critical downstream regulators in response to integrin ligation. These results provide genetic evidence for a critical role of SLP-76 in the regulation of neutrophil function.

Original languageEnglish
Pages (from-to)761-769
Number of pages9
JournalImmunity
Volume19
Issue number5
StatePublished - Nov 2003
Externally publishedYes

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    Newbrough, S. A., Mocsai, A., Clemens, R. A., Wu, J. N., Silverman, M. A., Singer, A. L., Lowell, C. A., & Koretzky, G. A. (2003). SLP-76 regulates Fcγ receptor and integrin signaling in neutrophils. Immunity, 19(5), 761-769.