A novel role for E- and P-selectins: shape control of endothelial cell monolayers.
The migration of neutrophils from blood vessels to peripheral tissues is a key step of inflammation. This requires the formation of transient gaps between endothelial cells with concomitant leucocyte squeezing through these narrow apertures and immediate restoration of endothelium continuity. It is currently considered that the main role of selectins is to mediate the initial contact between flowing leucocytes and endothelial cells. We show here that the binding of E- or P-selectins by specific antibodies induces a marked 'rounding up' of interleukin-1- or thrombin-activated human endothelial cells, respectively. Also, anti-E-selectin antibodies trigger a transient increase in cytosolic calcium involving intracellular calcium stores. No such effect is observed when von Willebrand factor or intercellular adhesion molecule 1 are similarly bound. Thus, in addition to promoting the initial interaction between activated endothelium and moving leucocytes, selectins might play a role in the induction of subsequent endothelial deformation, which would facilitate leucocyte arrest and transmigration towards peripheral tissues, and enhance the diffusion of soluble molecules between intravascular and peripheral compartments. Our results are consistent with this hypothesis and demonstrate a new property of endothelial selectins.
Kaplanski
G
G
INSERM U 387, Hôpital de Sainte-Marguerite, Marseille, France.
Farnarier
C
C
Benoliel
A M
AM
Foa
C
C
Kaplanski
S
S
Bongrand
P
P
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D002465:Cell Movement; D048429:Cell Size; D002478:Cells, Cultured; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D018799:Intercellular Adhesion Molecule-1 / Q000494:pharmacology; D007365:Intercellular Junctions; D007375:Interleukin-1 / Q000494:pharmacology; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology; D014471:Umbilical Veins; D014841:von Willebrand Factor / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007375:Interleukin-1; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D013917:Thrombin; D002118:Calcium