Separable requirements for cytoplasmic domain of PSGL-1 in leukocyte rolling and signaling under flow

Jonathan J. Miner, Lijun Xia, Tadayuki Yago, J. Kappelmayer, Zhenghui Liu, Arkadiusz G. Klopocki, Bojing Shao, J. Michael McDaniel, Hendra Setiadi, David W. Schmidtke, Rodger P. McEver

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

In inflamed venules, leukocytes use P-selectin glycoprotein ligand-1 (PSGL-1) to roll on P-selectin and E-selectin and to activate integrin αLβ2 (lymphocyte function-associated antigen-1, LFA-1) to slow rolling on intercellular adhesion molecule-1 (ICAM-1). Studies in cell lines have suggested that PSGL-1 requires its cytoplasmic domain to localize in membrane domains, to support rolling on P-selectin, and to signal through spleen tyrosine kinase (Syk). We generated "ΔCD" mice that express PSGL-1 without the cytoplasmic domain. Unexpectedly, neutrophils from these mice localized PSGL-1 normally in microvilli, uropods, and lipid rafts. ΔCD neutrophils expressed less PSGL-1 on their surfaces because of inefficient export from the endoplasmic reticulum. Limited digestion of wild-type neutrophils with O-sialoglycoprotein endopeptidase was used to reduce the PSGL-1 density to that on ΔCD neutrophils. At matched PSGL-1 densities, both δCD and wild-type neutrophils rolled similarly on P-selectin. However, ΔCD neutrophils rolling on P-selectin did not trigger Sykdependent activation of LFA-1 to slow rolling on ICAM-1. These data demonstrate that the PSGL-1 cytoplasmic domain is dispensable for leukocyte rolling on P-selectin but is essential to activate β2 integrins to slow rolling on ICAM-1.

Original languageEnglish
Pages (from-to)2035-2045
Number of pages11
JournalBlood
Volume112
Issue number5
DOIs
Publication statusPublished - Sep 1 2008

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Leukocyte Rolling
P-Selectin
Neutrophils
Intercellular Adhesion Molecule-1
Lymphocyte Function-Associated Antigen-1
Integrins
E-Selectin
Venules
P-selectin ligand protein
Microvilli
Endoplasmic Reticulum
Protein-Tyrosine Kinases
Digestion
Leukocytes
Chemical activation
Cells
Membranes
Lipids
Cell Line

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Separable requirements for cytoplasmic domain of PSGL-1 in leukocyte rolling and signaling under flow. / Miner, Jonathan J.; Xia, Lijun; Yago, Tadayuki; Kappelmayer, J.; Liu, Zhenghui; Klopocki, Arkadiusz G.; Shao, Bojing; McDaniel, J. Michael; Setiadi, Hendra; Schmidtke, David W.; McEver, Rodger P.

In: Blood, Vol. 112, No. 5, 01.09.2008, p. 2035-2045.

Research output: Contribution to journalArticle

Miner, JJ, Xia, L, Yago, T, Kappelmayer, J, Liu, Z, Klopocki, AG, Shao, B, McDaniel, JM, Setiadi, H, Schmidtke, DW & McEver, RP 2008, 'Separable requirements for cytoplasmic domain of PSGL-1 in leukocyte rolling and signaling under flow', Blood, vol. 112, no. 5, pp. 2035-2045. https://doi.org/10.1182/blood-2008-04-149468
Miner, Jonathan J. ; Xia, Lijun ; Yago, Tadayuki ; Kappelmayer, J. ; Liu, Zhenghui ; Klopocki, Arkadiusz G. ; Shao, Bojing ; McDaniel, J. Michael ; Setiadi, Hendra ; Schmidtke, David W. ; McEver, Rodger P. / Separable requirements for cytoplasmic domain of PSGL-1 in leukocyte rolling and signaling under flow. In: Blood. 2008 ; Vol. 112, No. 5. pp. 2035-2045.
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