Endothelial iNOS versus platelet iNOS: responsibility for the platelet/leukocyte endothelial cell interaction in murine antigen induced arthritis in vivo.
OBJECTIVE
Since an increase of platelet-endothelial cell interactions has been observed in mice with Antigen- induced-Arthritis (AiA) as well as an increase of NO expression, the aim of our study was to investigate in vivo the influence of NO, especially the platelet and endothelial inducible NO Synthase, on the platelet- and leukocyte endothelial cell interaction.


METHODS
C57/Bl6 mice and iNOS deficient mice were disposed in 6 groups (each=7). After induction of AiA, rolling and adherent fluorescence labelled platelets and leukocytes were investigated by intravital microscopy (IVM) on day 8 after AiA. Rank SUM Test and ANOVA on ranks have been performed regarding the data.


RESULTS
All arthritic mice presented an increase in platelet and leukocyte interaction with the endothelium compared to control groups. The arthritic iNOS deficient mice showed a more intense interaction of platelets and leukocytes with the endothelium in comparison with the wild-type arthritic mice. The group using arthritic wild-type recipient and iNOS deficient donor mice showed an increase in cell-interactions, leading to an endothelial effect, compared to the group using iNOS deficient arthritic recipient and wild-type donor mice.


CONCLUSIONS
The IVM data lead to an anti-inflammatory effect of NO, since NO followed an increase in platelet- and leukocyte- endothelial cell interaction in iNOS deficient mice with AiA. In addition, we have shown for the first time in vivo that platelet NO produced by iNOS seems to have a minor influence on the leukocyte induced tissue damage in contrast to endothelial iNOS. Therefore, selective platelet inhibition would not interfere with the protective effect of NO.
Schmitt-Sody
M
M
Department of Orthopaedics, Ludwig Maximilians University of Munich, Klinikum Grosshadern, Marchioninistr. 15, 81377 Munich, Germany. marcus.schmitt-sody@med.uni-muenchen.de
Gottschalk
O
O
Metz
P
P
Zysk
S
S
Hausdorf
J
J
von Schulze Pellengahr
C
C
Veihelmann
A
A
Jansson
V
V
D000818:Animals; D000941:Antigens / Q000737:chemistry; D001168:Arthritis / Q000139:chemically induced*; D001792:Blood Platelets / Q000201:enzymology* / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D004727:Endothelium / Q000201:enzymology*; D007962:Leukocytes / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D008853:Microscopy; D008856:Microscopy, Fluorescence; D015233:Models, Statistical; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D013997:Time Factors
D000941:Antigens; D052247:Nitric Oxide Synthase Type II