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

doi:10.1016/s1074-7613(03)00305-4

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

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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 language	English
Pages (from-to)	761-769
Number of pages	9
Journal	Immunity
Volume	19
Issue number	5
DOIs	https://doi.org/10.1016/s1074-7613(03)00305-4
State	Published - Nov 2003

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@article{0771da3b836e44c28262d861fef23a69,

title = "SLP-76 regulates Fcγ receptor and integrin signaling in neutrophils",

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.",

author = "Newbrough, {Sally A.} and Attila Mocsai and Clemens, {Regina A.} and Wu, {Jennifer N.} and Silverman, {Michael A.} and Singer, {Andrew L.} and Lowell, {Clifford A.} and Koretzky, {Gary A.}",

note = "Funding Information: We thank Rich Schretzenmair and the Abramson Cancer Center Flow Cytometry and Cell Sorting Shared Resource for their expertise and ingenuity in flow cytometry. We thank M. Jordan, K. Nichols, E. Peterson, and J. Stadanlick for critical reading of the manuscript. This work was supported in part by grants from the American Heart Association (S.D.) and NIH (G.K., J.W., and C.L.).",

year = "2003",

month = nov,

doi = "10.1016/s1074-7613(03)00305-4",

language = "English",

volume = "19",

pages = "761--769",

journal = "Immunity",

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T1 - SLP-76 regulates Fcγ receptor and integrin signaling in neutrophils

AU - Newbrough, Sally A.

AU - Mocsai, Attila

AU - Clemens, Regina A.

AU - Wu, Jennifer N.

AU - Silverman, Michael A.

AU - Singer, Andrew L.

AU - Lowell, Clifford A.

AU - Koretzky, Gary A.

N1 - Funding Information: We thank Rich Schretzenmair and the Abramson Cancer Center Flow Cytometry and Cell Sorting Shared Resource for their expertise and ingenuity in flow cytometry. We thank M. Jordan, K. Nichols, E. Peterson, and J. Stadanlick for critical reading of the manuscript. This work was supported in part by grants from the American Heart Association (S.D.) and NIH (G.K., J.W., and C.L.).

PY - 2003/11

Y1 - 2003/11

N2 - 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.

AB - 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.

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U2 - 10.1016/s1074-7613(03)00305-4

DO - 10.1016/s1074-7613(03)00305-4

M3 - Article

C2 - 14614862

AN - SCOPUS:30144435908

SN - 1074-7613

VL - 19

SP - 761

EP - 769

JO - Immunity

JF - Immunity

IS - 5

ER -

SLP-76 regulates Fcγ receptor and integrin signaling in neutrophils

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