T-cell interaction with ICAM-1/ICAM-2 double-deficient brain endothelium in vitro: the cytoplasmic tail of endothelial ICAM-1 is necessary for transendothelial migration of T cells.
Endothelial intercellular adhesion molecule 1 (ICAM-1) and ICAM-2 are both involved in lymphocyte extravasation during immunosurveillance and inflammation. To define their exact role during T-cell extravasation, we used mouse T cells and ICAM-1-/-ICAM-2-/- brain endothelioma cells. ICAM-1-/-ICAM-2-/- brain endothelioma cells did not support transendothelial migration (TEM) of T cells in vitro. Re-expression of different ICAM-1 mutants in the ICAM-1-/-ICAM-2-/- endothelioma line bEndI1/2.1 or in the ICAM-1-/- endothelioma line bEndI1.1 demonstrated that the extracellular domain of ICAM-1 suffices to support T-cell adhesion while the presence of the cytoplasmic tail was strictly required for TEM. Surprisingly, tyrosine phosphorylation of endothelial ICAM-1 was not necessary for TEM of T cells or for Rho guanosine triphosphatase (RhoGTPase) activation. Furthermore, cytoplasmic deletion mutants of ICAM-1 were unable to mediate RhoGTPase activation. Thus, our data demonstrate that the cytoplasmic tail of endothelial ICAM-1-independently from tyrosine phosphorylation-is essential for supporting TEM of T lymphocytes, while Rho signaling is involved in endothelial cells.
Lyck
Ruth
R
Max-Planck-Institute for Physiological and Clinical Research, W G Kerckhoff Institute, Bad Neuheim, Germany.
Reiss
Yvonne
Y
Gerwin
Nicole
N
Greenwood
John
J
Adamson
Peter
P
Engelhardt
Britta
B
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000166:cytology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D004730:Endothelium, Vascular / Q000166:cytology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C480027:ICAM-2 protein, mouse; D018799:Intercellular Adhesion Molecule-1; D020741:rho GTP-Binding Proteins