concanavalin-a and Osteoarthritis

Topics: Acute-Phase Proteins; alpha 1-Antichymotrypsin; C-Reactive Protein; Concanavalin A; Humans; Immunoelectrophoresis; Inflammation; Orosomucoid; Osteoarthritis; Pain Measurement

A system has been established to assess the recruitment of 99mTc-hexamethylpropylene amine oxamine (99mTc-HMPAO)-labelled PBMC and [125I]iododeoxyuridine-labelled Con A stimulated lymphoblasts to allogeneic human synovial xenografts in the ears of SCID mice. Successful engraftment of osteoarthritic synovium was achieved in approximately 90% of cases and a connection between the human microvasculature of the xenograft and the circulation of the mouse was shown. Cells were delivered to the xenograft by a system of regional vascular perfusion, thus avoiding the major murine vascular beds. The accumulation of 99mTc-HMPAO-labelled PBMC in mouse ears was monitored in real time. Direct injection of xenograft-bearing ears with recombinant human TNF-alpha, 7 h prior to perfusion, increased the accumulation of both PBMC and lymphoblasts in cytokine-injected ears compared to contralateral control-injected ears. Autoradiography revealed the presence of [125I]iododeoxyuridine-labelled lymphoblasts associated with human microvasculature within the xenograft. However, the increased accumulation of lymphoblasts in cytokine-injected ears occurred in the tissues surrounding the xenograft, where lymphoblasts were associated more often with murine than human vessels. Although the system described offers advantages over similar models, the propensity for mouse endothelium to interact with human leucocytes is likely to be a generic disadvantage for models of human leucocyte recruitment to xenografts in immunodeficient mice.

Topics: Animals; Autoradiography; Concanavalin A; Ear; Female; Humans; Idoxuridine; Immunohistochemistry; Intercellular Adhesion Molecule-1; Iodine Radioisotopes; Leukocytes, Mononuclear; Lymphocyte Activation; Lymphocytes; Male; Mice; Mice, SCID; Organotechnetium Compounds; Osteoarthritis; Oximes; Perfusion; Recombinant Proteins; Synovial Membrane; Technetium Tc 99m Exametazime; Transplantation, Heterologous; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

The integrity of cartilage matrix depends on the homeostasis of synthetic and degradative processes. Any disturbance of the rate of synthesis and catabolism may alter the amount of matrix components (e.g. proteoglycans). Based upon a biochemically induced osteoarthrosis (OA) in the knee joints of rats we investigated the histomorphological alterations under therapy with diclofenac sodium by histological-histochemical grading. Lectin-binding techniques using labelled wheat germ agglutinin (WGA), concanavalin A (Con A), Ulex europeus agglutinin I (UEA I), soybean agglutinin (SBA), and peanut agglutinin (PNA) were applied to analyze the cellular as well as the extracellular glycoconjugates in situ. Lectin-binding patterns quantitatively describe the topographical localization of structural components of the cartilage matrix which carry certain sugar residues. The therapy of the experimental OA with diclofenac sodium (2.0 mg/kg s.c.) led to a marked reduction of cartilage degenerations. Our results indicate antidegenerative properties of this compound. These findings are consistent with the fluorescent analytical data which show a stimulating effect on the anabolic activity of chondrocytes in the osteoarthritic joints under the treatment with diclofenac sodium. Fluorescein isothiocyanate labelled lectins are useful histochemical tools to determine alterations in the integrity of cartilage by their specific binding patterns, because zonal differentiation in physiological function and morphological structure of cartilage tissue as well as cellular, pericellular, and interterritorial local events are characterized.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cartilage; Concanavalin A; Diclofenac; Histocytochemistry; Lectins; Male; Osteoarthritis; Rats; Rats, Inbred Strains; Wheat Germ Agglutinins

The development of osteoarthrotic cartilage lesions in the knee joints of male STR/IN mice was studied with respect to their histologic appearance and their various localizations in the joint. Spontaneous articular cartilage degeneration on the medial portion of the tibial plateau was considered to be the initial event. Continued loss of cartilage subsequently led to a pronounced instability of the knee joint, with a varus deformity. This was followed by medial patellar luxation with corresponding osteoarthrotic lesions at the facies patellaris femoris. The most marked osteoarthrotic cartilage degeneration developed on the medial tibial condyle and at the facies patellaris femoris of the femoropatellar joint. Histologic examination of the osteoarthrotic defects in these two regions revealed distinct morphologic differences with respect to formation of chondrocyte clusters, tendency to regeneration, and proliferation reactions. Lectin binding experiments in normal articular cartilage revealed regional differences regarding the presence or absence of keratan sulfate in the extracellular matrix. The lack of keratan sulfate in tibial cartilage might reflect its tendency to degenerate spontaneously. It is therefore suggested that male STR/IN mice are particularly useful for studying two different types of osteoarthrosis, one due to a biomechanically induced instability (patellar luxation) and one due to biochemical changes (absence of keratan sulfate) of still unknown pathogenesis.

Topics: Animals; Cartilage, Articular; Concanavalin A; Femur; Knee Joint; Male; Mice; Mice, Inbred Strains; Osteoarthritis; Tibia; Wheat Germ Agglutinins