TY - JOUR
T1 - The PSGL-1-L-selectin signaling complex regulates neutrophil adhesion under flow
AU - Stadtmann, Anika
AU - Germena, Giulia
AU - Block, Helena
AU - Boras, Mark
AU - Rossaint, Jan
AU - Sundd, Prithu
AU - Lefort, Craig
AU - Fisher, Charles I.
AU - Buscher, Konrad
AU - Gelschefarth, Bernadette
AU - Urzainqui, Ana
AU - Gerke, Volker
AU - Ley, Klaus
AU - Zarbock, Alexander
PY - 2013/10
Y1 - 2013/10
N2 - Neutrophils are recruited from the blood to sites of inflammation, where they contribute to immune defense but may also cause tissue damage. During inflammation, neutrophils roll along the microvascular endothelium before arresting and transmigrating. Arrest requires conformational activation of the integrin lymphocyte function-associated antigen 1 (LFA-1), which can be induced by selectin engagement. Here, we demonstrate that a subset of P-selectin glycoprotein ligand-1 (PSGL-1) molecules is constitutively associated with L-selectin. Although this association does not require the known lectin-like interaction between L-selectin and PSGL-1, the signaling output is dependent on this interaction and the cytoplasmic tail of L-selectin. The PSGL-1-L-selectin complex signals through Src family kinases, ITAM domain-containing adaptor proteins, and other kinases to ultimately result in LFA-1 activation. The PSGL-1-L-selectin complex-induced signaling effects on neutrophil slow rolling and recruitment in vivo demonstrate the functional importance of this pathway. We conclude that this is a signaling complex specialized for sensing adhesion under flow.
AB - Neutrophils are recruited from the blood to sites of inflammation, where they contribute to immune defense but may also cause tissue damage. During inflammation, neutrophils roll along the microvascular endothelium before arresting and transmigrating. Arrest requires conformational activation of the integrin lymphocyte function-associated antigen 1 (LFA-1), which can be induced by selectin engagement. Here, we demonstrate that a subset of P-selectin glycoprotein ligand-1 (PSGL-1) molecules is constitutively associated with L-selectin. Although this association does not require the known lectin-like interaction between L-selectin and PSGL-1, the signaling output is dependent on this interaction and the cytoplasmic tail of L-selectin. The PSGL-1-L-selectin complex signals through Src family kinases, ITAM domain-containing adaptor proteins, and other kinases to ultimately result in LFA-1 activation. The PSGL-1-L-selectin complex-induced signaling effects on neutrophil slow rolling and recruitment in vivo demonstrate the functional importance of this pathway. We conclude that this is a signaling complex specialized for sensing adhesion under flow.
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U2 - 10.1084/jem.20130664
DO - 10.1084/jem.20130664
M3 - Article
C2 - 24127491
AN - SCOPUS:84886823023
SN - 0022-1007
VL - 210
SP - 2171
EP - 2180
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 11
ER -