Selective inhibition of platelets by the GPIIb/IIIa receptor antagonist Tirofiban reduces leukocyte-endothelial cell interaction in murine antigen-induced arthritis.
OBJECTIVE
Inflammation is associated with the invasion of leukocytes into affected tissues and with the up-regulation of platelet activation and adhesion. Assuming that leukocyte accumulation is linked to platelet aggregation, the aim of our study was to examine the effects of selective platelet inhibition by the glycoprotein (GP) IIb/IIIa receptor antagonist Tirofiban on the leukocyte-endothelial cell interaction.


METHODS
We used the model of antigen-induced arthritis (AiA) to induce inflammatory changes in the synovial microcirculation. Ex vivo labelled platelets and in vivo fluorescence-labelled leukocytes were visualized by intravital microscopy (IVM). C57/Bl6 mice were allocated to four groups; two control groups with saline or Tirofiban and two groups with AiA that also received either saline or Tirofiban (0.5 microg/g BW) intravenously.


RESULTS
There was no significant change in platelet- or leukocyte- endothelial cell interaction in the endothelium in healthy control animals. In contrast, after selective inhibition of platelets, the platelet- and leukocyte-endothelial cell interaction was significantly reduced in arthritic mice and reached the level of the healthy control groups.


CONCLUSIONS
Selective platelet inhibition by Tirofiban resulted in reduced leukocyte-endothelial cell interactions in AiA. Consequently, platelets contribute to leukocyte adhesion in AiA via GPIIb/IIIa and therefore platelet inhibition could become an additional therapy option in chronic arthritic disease.
Schmitt-Sody
M
M
Department of Orthopaedics, Klinikum Grosshadern, Ludwig-Maximilians-University, Marchioninistr. 15, 81377, Munich, Germany. marcus.schmitt-sody@med.uni-muenchen.de
Metz
P
P
Gottschalk
O
O
Zysk
S
S
Birkenmaier
C
C
Goebl
M
M
von Schulze Pellengahr
C
C
Veihelmann
A
A
Jansson
V
V
D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy*; D002450:Cell Communication / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D005260:Female; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D000077466:Tirofiban