Induced changes of leukocyte slow rolling in an in flow pharmacological model of adhesion to endothelial cells.
BACKGROUND
Rolling of leukocytes at the surface of the vascular endothelium is a prerequisite for a subsequent firm adhesion, particularly the slow rolling appearing on ELAM CD62E. Therefore, it may be considered that increasing the rolling velocities should be a precise therapeutic target in clinical situations where leukocytes accumulate, mainly venous and arterial ischaemia.


METHODS
Human neutrophils were allowed to flow on endothelial HUVECs, with and without 4 hours interleukin-1alpha activation, the cells having or not been incubated with INO5042 anti-inflammatory drug. Under a mean shear-stress of 2 dyn/cm(2), rollers and stickers were identified and quantified, using a video-camera and picture analysing software.


RESULTS
When the drug had been added to endothelial cells a shift of velocities was observed towards fast speeds (from 3-5 to 7-11 microm/sec). The same results was significantly found when neutrophils, alone or along with endothelium, had been submitted to the drug, the number of stickers and rollers beeing reduced as well. Finally, such a precise pharmacological method proved efficient to detect the exact mechanism of INO5042 on white cell adhesion.
Renard
M
M
University Victor Segalen Bordeaux 2, Bordeaux, France & Innothera Biological Research Department, Paris-Arcueil, Paris, France. martine.renard@hemato.u-bordeaux2.fr
Heutte
F
F
Boutherin-Falson
O
O
Finet
M
M
Boisseau
M R
MR
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D018929:Cell Culture Techniques; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D036904:Leukocyte Rolling / Q000187:drug effects / Q000502:physiology*; D018715:Microscopy, Video; D008954:Models, Biological; D018375:Neutrophil Activation / Q000502:physiology; D009504:Neutrophils / Q000502:physiology
D000893:Anti-Inflammatory Agents; D019040:E-Selectin; D007375:Interleukin-1