Abstract
A novel model for the investigation of the microcirculation in synovial tissue of the mouse knee joint is presented. The mouse knee joint was exposed on a specially designed plexiglass stage with a slight flexion. After partial resection of the skin, the patella tendon was cut transversally, which allowed for visualization of the “Hoffa’s fatty body”, an intraarticular fatty tissue containing synovial cells on the interior surface of the joint. An intravital fluorescence microscope was adjusted to observe the microcirculation of this intraarticular synovial tissue without opening of the joint capsula. For staining of the plasma, fluorescein isothiocyanate (FITC)-dextran was used, and for the staining of leukocytes rhodamine 6G was used. The tissue investigated presents with a high-density honeycomb-like capillary network, containing some postcapillary venules and a few arterioles. The following parameters were assessed off-line using a computer-assisted microcirculation analysis system: flow and diameter of arterioles and postcapillary venules, as well as functional capillary density. Moreover, leukocyte-endothelial cell interaction was quantified by counting the number of rolling cells and cells adhering to the endothelium in postcapillary venules. As an indication of endothelial leakage, macromolecular extravasation was also assessed. To validate the model, we investigated these parameters at three time points during an observation period of 60 min. There was no change in functional capillary density, nor in vessel diameter after 60 min of observation. Moreover, there was neither a change in the number of rolling cells, nor in the number of cells adhering to the endothelium nor in extravasation of FITC-dextran, thus indicating the stability of the preparation. The new model allows the quantitative analysis of the intraarticular microcirculation of the synovial fatty tissue in vivo. It provides insight into the dynamics of synovial microcirculation and leukocyteendothelial cell interaction in acute or chronic joint inflammation.
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References
Bohlen HG, Gore RW (1976) Preparation of rat intestinal muscle and mucosa for quantitative microcirculatory studies. Microvasc Res 11:103-110
Brackerts D, Mitchell GF, Mackay IR (1977) Antigen-induced arthritis in various strains of mice. Arthritis Rheum 20:841-850
Endrich B, Asaishi K, Götz A, Messmer K (1980) Technical report - a new chamber technique for microvascular studies in unanethetized hamsters. Res Exp Med 177:125-134
Funk RHW, Tischendorf R, Bratengeier H (1995) Microendoscopy of the synovial vasculature in the rabbit knee joint. Microvasc Res 50:45-55
Granger DN, Kubes P (1994) The microcirculation and inflammation: modulation of leukocyte-endothelial cell adhesion. J Leukoc Biol 55:662-675
Grober JS, Bowen BL, Ebling H, Athey B, Thompson CB, Fox DA (1993) Monocyteendothelial adhesion in chronic rheumatoid arthritis. J Clin Invest 91:2609-2619
Harris AG, Leiderer R, Peer F, Messmer K (1996) Skeletal muscle microvascular and tissue injury after varing durations of ischemia. Am J Physiol 271:H2388-H2398
Harris AG, Hecht R, Peer F, Nolte D, Messmer K (1997) An improved intravital microscopy system. Int J Microcirc Clin Exp 17:322-327
Hempfling H (1996) Mikroarthroendoskopie. Arthroskopie 9:106-115
Issekutz TB, Miyasaka M, Issekutz AC (1996) Rat blood neutrophils express very late antigen 4 and it mediates migration to arthritic joint and dermal inflammation. J Exp Med 183:2175-2184
Johnston B, Issekutz TB, Kubes P (1995) The α4-integrin supports leukocyte rolling and adhesion in chronically inflamed postcapillary venules in vivo. J Exp Med 183:1995-2006
Kurose I, Kubes P, Wolf R, Anderson DC, Paulson J, Miyasaka M (1993) Inhibition of nitric oxide production. Circ Res 73:164-171
Lehr HA, Leunig M, Menger MD, Nolte D, Messmer K (1993) Dorsal skinfold chamber technique for intravital microscopy in nude mice. Am J Pathol 143:1055-1062
Levick JR (1995) Microvascular architecture and exchange in synovial joints. Microcirculation 2:217-233
McCartney-Francis N, Allen JB, Mizel DE, Albina JE, Xie Q, Nathan CF (1993) Suppression of arthritis by an inhibitor of nitric oxide synthase. J Exp Med 178:749-754
Menger MD, Lehr HA (1993) Scope and perspectives of intravital microscopy. bridge over from in vitro to in vivo. Immunol Today 14:519-522
Menger MD, Vollmar B (1996) Adhesion molecules as determinants of disease: from molecular biology to surgical research. Br J Surg 83:588-601
Muller WA (1995) The role of PECAM-1 (CD31) in leukocyte emigration: studies in vitro and in vivo. J Leukoc Biol 57:523-528
Nolte D, Hecht R, Schmid P, Botzlar, Menger MD, Neumueller C, Sinowatz F, Vestweber D, Messmer K (1994) Role of Mac-1 and ICAM-1 in ischemia-reperfusion injury in a microcirculation model of BALB/C mice. Am J Physiol 267:H1320-H1328
Nolte D, Schmid P, Jager U, Botzlar A, Roesken F, Hecht R, Uhl E, Messmer K, Vestweber D (1994) Leukocyte rolling in venules of striated muscle and skin is mediated by P-selectin, not by L-selectin. Am J Physiol 267:H1637-H1642
Schaible UE, Vestweber D, Butcher EG, Stehle T, Simon MM (1994) Expression of endothelial cell adhesion molecules in joints and heart during Borrelia burgdorferi infection of mice. Cell Adhes Commun 2:465-479
Steinbauer M, Harris AG, Messmer K (1997) Effects of dextran on microvascular ischemia-reperfusion injury in striated muscle. Am J Physiol 272:H1710-H1716
Tillmanns H, Neumann FJ, Tiefenbacher C, Dorigo O, Parekh N, Waas W, Zimmermann R, Steinhausen M, Kuebler W (1993) Activation of neutrophils in the microvasculature of the ischaemic and reperfused myocardium. Eur Heart J 14 [Suppl 1]:82-86
Veihelmann A, Brill T, Blobner M, Scheller I, Mayer B, Stadler J (1997) Inhibition of nitric oxide improves detoxification in inflammatory liver dysfunction in vivo. Am J Physiol 36:G530-G537
Villringer A, Haberl RL, Dirnagl U, Anneser F, Verst M, Einhaupl KM (1989) Confocal laser microscopy to study microcirculation on the rat brain surface in vivo. Brain Res 504:159-160
Vollmar B, Lang G, Post S, Menger MD, Messmer K (1993) Microcirculation of the liver in hemorrhagic shock in the rat and its significance for energy metabolism and function. Zentralbl Chir 118:218-225
Vollmar B, Ruttinger D, Wanner GA, Leiderer R, Menger MD (1996) Modulation of Kupffer cell activity by gadolinium chloride in endotoxemic rats. Shock 6:434-441
Wakelin MW, Sanz MJ, Dewar A, Albeda SM, Larkin SW, Boughton-Smith N, Williams TJ, Nourshargh S (1996) An anti-platelet-endothelial cell adhesion molecule-1 antibody inhibits leukocyte extravasation from mesenteric microvessels in vivo by blocking the passage through the basement membrane. J Exp Med 184:229-239
Zeintl H, Sack F-U, Intaglietta M, Messmer K (1989) Computer assisted leukocyte velocity measurements in intravital microscopy. Int J Microcirc Clin Exp 8:293-302
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Veihelmann, A., Szczesny, G., Nolte, D. et al. A novel model for the study of synovial microcirculation in the mouse knee joint in vivo. Res. Exp. Med. 198, 43–54 (1998). https://doi.org/10.1007/s004330050088
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DOI: https://doi.org/10.1007/s004330050088