VOL. 3, No. 2, April 2006

M. Löhn, et al. [2006] Med Hypotheses Res 3: 687-698.

PSGL-1 Induces Opening of Chloride Channels and
Changes in Cell Volume via Tyrosine Phosphorylation

Matthias Löhn*, Rostislav Bychkov, Michael Fürstenau, Faikah
Abou-Rebyeh, Petra Quass, Carsten Lindschau, Ekkehard Ziegler,
Ulrich Kunzendorf, Maik Gollasch, Friedrich C. Luft and Hermann

Department of Nephrology, Medical School Hannover, Hannover, Germany (M.L., F.A.B.,
C.L., H.H.), Franz-Volhard-Clinic at the Max-Delbrück-Center for Molecular Medicine
(R.B., F.C.L), and Department of Nephrology, Medical Clinic IV, Erlangen-Nürnberg (E.Z.,

Abstract. Leukocyte binding to endothelial surface adhesion molecules is an important
early step in inflammation, which is mediated initially by the interaction of the P-selectin
with its ligand (PSGL-1). We investigated the intracellular signal transduction of PSGL-1
and tested the hypothesis that the binding of PSGL-1 may induce ion channel opening. We
used a chimeric protein consisting of the intracellular PSGL-1 domain and the Fc part of IgG
as the extracellular domain expressed in CHO cells. PSGL-1 ligation induced a rapid increase
in perimembranous and focal tyrosine phosphorylation and activated a current with a single
channel conductance of 27 pS. The current showed a shift of the reversal potential when
extracellular chloride was altered and was DIDS sensitive, indicating that PSGL-1 signaling
activates chloride channels. Changes in ion current were completely inhibited by tyrosine
kinase inhibition. Lastly, PSGL-1 induced a rapid decrease in cell volume, which was
inhibited by both, inhibition of tyrosine kinase and and inhibition of chloride channels. We
suggest that binding to PSGL-1 induces a decrease in cell size via a tyrosine
kinase-dependent opening of a chloride channel. Chloride channel activation may lead to cell
shrinkage and thereby modulate further cell adhesion.

*Address all correspondence to: Dr. M. Löhn, Sanofi-Aventis Deutschland GmbH,
Cardiovascular Diseases, Industriepark Hoechst, Building H821, D-65926 Frankfurt/Main
Germany. E-mail:

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