Visualization and in situ analysis of leukocyte trafficking into the ankle joint in a systemic murine model of rheumatoid arthritis.
OBJECTIVE
To describe the kinetics of leukocyte migration into a distal joint during the development of chronic inflammation in a murine model of rheumatoid arthritis (RA), to identify leukocyte subpopulations recruited in the synovial vessels, and to test in real time the effects of an antiinflammatory compound on leukocyte-endothelial cell interactions in the arthritic joint.


METHODS
We used intravital video microscopy (IVM), which was adapted to the microcirculation of the mouse ankle, to monitor the kinetics of leukocyte-endothelium interactions (rolling and firm adhesion) during the onset and progression of proteoglycan-induced arthritis (PGIA), a chronic autoimmune model of RA. Subpopulations of rolling and adherent leukocytes were identified by in vivo immunostaining. Leukocyte extravasation into the ankle joint was verified histologically.


RESULTS
Between the onset of arthritis and the beginning of the destructive phase of PGIA, we found a steady increase in the number of leukocytes that exhibited firm adherence to the endothelium of synovial vessels, which clearly underscores the chronic, self-perpetuating character of joint inflammation in this autoimmune model. We showed, however, that granulocytes, and not T cells, constituted the major cell population that was continuously recruited to the inflamed ankle. Using IVM, we could detect instant changes in leukocyte adhesion behavior in the synovial vessels of the arthritic joint upon administration of a compound that antagonizes leukocyte rolling.


CONCLUSIONS
IVM of the microcirculation of the mouse ankle could become an essential tool for investigating the mechanisms that regulate leukocyte migration to the joint in systemic models of RA as well as for preclinical testing of antiinflammatory therapies.
Gál
István
I
Rush University Medical Center, Chicago, Illinois 60612, USA.
Bajnok
Eva
E
Szántó
Sándor
S
Sarraj
Bara
B
Glant
Tibor T
TT
Mikecz
Katalin
K
D000818:Animals; D000843:Ankle Joint / Q000276:immunology / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology*; D002465:Cell Movement / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007700:Kinetics; D036904:Leukocyte Rolling / Q000187:drug effects / Q000276:immunology; D007962:Leukocytes / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018715:Microscopy, Video / Q000295:instrumentation / Q000379:methods*; D011134:Polysaccharides / Q000494:pharmacology
D000970:Antineoplastic Agents; D011134:Polysaccharides; C007789:fucoidan