Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The migration of T lymphocytes into arthritic joints of rats with adjuvant arthritis was examined and compared to the accumulation of the same cells in cutaneous inflammation, since previous studies had shown that only a subpopulation of T lymphocytes, found enriched in peritoneal exudates (sPEL), migrated efficiently to cutaneous inflammatory sites. Surprisingly, lymphocyte migration to the inflamed joint included T cells from most of the recirculating lymphocyte pool, including sPEL, spleen, peripheral lymph node (PLN), and Peyer's patches, and was much more rapid than migration through either cutaneous sites or PLNs. Treatment of sPEL with antibody to VLA-4 inhibited sPEL accumulation in the joints, while anti-VLA-4 treatment did not affect the accumulation of PLN T cells. It is concluded that the arthritic joint not only attracts inflammation-seeking lymphocytes (sPEL), through at least a partially VLA-4 dependent interaction, but also large numbers of lymphocytes which normally migrate to PLNs through a VLA-4-independent mechanism.
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PMID:T lymphocyte migration to arthritic joints and dermal inflammation in the rat: differing migration patterns and the involvement of VLA-4. 193 31

The angiogenesis inhibitor AGM-1470 has recently been reported to inhibit collagen-induced arthritis in rats. To determine if the anti-arthritic effects of AGM-1470 might be due to T cell inhibition, we have studied its effects on T cell responses in vitro. Responses of human cells to tetanus toxoid (TT), and those of murine splenocytes to staphylococcal enterotoxin (SE), mitogens or a mls difference were inhibited by AGM-1470. Responses of human cells to SE, OKT3 and PHA were all partially inhibited on day 2 (d2) but not d3, and in fact were augmented on d6-8. The amount of IL-2 in SEA cultures was augmented on d4 and d5. There were no differences in the expression of CD3, CD4, CD8, CD25, CD45RA, CD45RO, LFA-1, VLA-4 or VLA-6 in inhibited cultures, except for slight decreases in CD25 and CD45RO in TT cultures. These results indicated that the angiogenesis inhibitor AGM-1470 also modulates human and murine lymphocyte function.
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PMID:Modulation of T lymphocyte function by the angiogenesis inhibitor AGM-1470. 827 96

Adhesion molecules and cytokines are important in chronic inflammatory conditions such as rheumatoid arthritis (RA) by virtue of their role in cell activation and emigration. Using immunohistochemical techniques we studied the expression of adhesion molecules and cytokines in cryopreserved sections of murine knee joint in the course of antigen-induced arthritis, an animal model of human RA. Various adhesion molecules and cytokines are expressed in the arthritic joint tissue. LFA-1, Mac-1, CD44, ICAM-1 and P-selectin were strongly expressed in the acute phase and to a lesser degree in the chronic phase of arthritis. VLA-4 and VCAM-1 appeared to be moderately expressed on day 1, L-selectin between days 1 and 3. LFA-1, Mac-1, CD44, alpha 4-integrin, ICAM-1 and the selectins were found expressed on cells of the synovial infiltrate, LFA-1, Mac-1 and ICAM-1 on the synovial lining layer, and VCAM-1 and P-selectin on endothelial cells. Expression of E-selectin could be demonstrated throughout the experiment at a low level in cells of the acute cell infiltrate. Cytokines, especially IL-2, IL-4, IL-6, TNF, and IFN-gamma, were heavily expressed during the acute phase of arthritis in cellular infiltrate. Taken together these data demonstrate that cytokines and their activation of adhesion molecules contribute to cell infiltration and activation during the initial phase of arthritis and to the induction and progression of tissue destruction in arthritic joints. These molecules might be potential targets for novel therapeutic strategies in inflammatory and arthritic disorders.
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PMID:Expression of cell adhesion molecules and cytokines in murine antigen-induced arthritis. 975 22

Neutrophils, or polymorphonuclear leukocytes (PMNLs), migrate through vascular endothelium and in connective tissue during inflammation. In rats with adjuvant arthritis, migration to joints of radiolabeled (111In) blood PMNLs was examined to define the role of specific selectin and integrin adhesion molecules in this process. Based on monoclonal antibody studies, P-selectin was required for normal PMNL migration to the joints. Although E-selectin alone was not essential, it mediated PMNL accumulation when the P-selectin mechanism was blocked. However, 30% to 40% of the PMNL accumulation was L-, P-, and E-selectin-independent. The integrins, LFA-1 and Mac-1 (CD11/CD18), and VLA-4 mediated PMNL migration to arthritic joints. However, 20% to 40% of PMNL accumulation was via CD18- and VLA-4-independent mechanisms. Human PMNL migration in vitro across unstimulated human umbilical vein endothelial cells (HUVEC), induced by C5a or IL-8, was virtually all mediated by the CD18 (beta2) integrins, LFA-1 and Mac-1. PMNL transendothelial migration was partly CD18-independent (35%) when endothelium was activated with cytokines, such as interleukin-1, and a chemotactic gradient, such as C5a, was also present. This CD18-independent migration was partially E-selectin-dependent in vitro. PMNL migration across synovial fibroblasts induced by C5a was mediated by Mac-1, VLA-4, VLA-5, and VLA-6, functioning in concert. However, up to 30% of migration was via mechanisms as yet to be defined. Thus, PMNL transendothelial and extravascular migration involves some shared, and some distinct mechanisms, as well as some yet to be identified. Defining these mechanisms may help develop therapies for controlling PMNL involvement in inflammation in the vascular and extravascular spaces.
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PMID:Adhesion molecules mediating neutrophil migration to arthritis in vivo and across endothelium and connective tissue barriers in vitro. 983 14

Neutrophil migration from blood into inflamed tissues is mediated by adhesion molecules on neutrophils and on vascular endothelium. It was previously shown that the integrins VLA-4 and CD11/CD18 in combination mediate 70-80% of neutrophil recruitment to arthritic joints of rats. To investigate if the remaining recruitment involves the selectins, the effect of adhesion-blocking monoclonal antibodies (mAb) to each of the selectins (E-, P and L-), in combination with mAb to VLA-4 and CD18, on the migration of radiolabeled neutrophils to joints of rats with adjuvant arthritis was examined. Blocking P-selectin inhibited neutrophil accumulation in hindlimb joints by 40% whereas mAb to P- and E-selectin together inhibited the accumulation in all joints by 60% relative to anti-VLA-4 plus anti-CD18 treatment alone. Overall there was 90% inhibition relative to arthritic controls. Blocking E- or L-selectin alone or together had no effect. Our results demonstrate that P-selectin in particular and in concert with E-selectin are required for the VLA-4- and CD18-independent migration of neutrophils to sites of chronic arthritis in the rat.
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PMID:The role of selectins in VLA-4 and CD18-independent neutrophil migration to joints of rats with adjuvant arthritis. 1022 75

DBA/1LacJ mice were immunized with type II collagen and boosted with bacterial lipopolysaccharide (LPS) 17 days later to induce accelerated arthritis. Clinical signs of inflammation were observed as early as Day 20. Matrix metalloproteinases MMP-2, -3, -9, and -13, but not MMP-12, mRNA levels were increased on Day 24. Administration of anti-VLA-4 antibody (mAb; 8 mg/kg/day for 3 days) at the time of LPS treatment strikingly inhibited arthritis-induced paw inflammation and histological scores, but not the increase in MMP expression. A higher dose of mAb (20 mg/kg/day for 4 days) inhibited pathology and normalized the levels of MMP mRNAs. In conclusion, the pathophysiology of this accelerated model of arthritis is VLA-4-dependent, and VLA-4-mediated events have a role in inflammation-induced MMP expression. Inhibition of arthritis-induced increases in MMP expression is not necessary to reduce pathology. This model is well suited for identifying agents that block integrin VLA-4 in vivo.
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PMID:Blockade of integrin VLA-4 prevents inflammation and matrix metalloproteinase expression in a murine model of accelerated collagen-induced arthritis. 1279 50

The role of the integrins VLA-4 and LFA-1 and of the selectin adhesion molecules in autoimmune arthritis was investigated. Adjuvant arthritis was induced in Lewis rats by active immunization (s.c.) with Mycobacterium butyricum or by adoptive transfer of immune T cells. With active adjuvant arthritis, Lewis rats develop maximal polyarticular joint inflammation and migration of radiolabelled (111In and 51Cr) blood neutrophils and monocytes to the joints 14 days post Mycobacterium butyricum immunization. Using blocking monoclonal antibodies we osbserved that at this stage monocyte recruitment was dependent (85%) on P-selectin plus VLA-4 (alpha4B1) and neutrophil recruitment depended (> 80%) on P-selectin plus LFA-1 (CD11a/CD18). E-selectin played a minimal role in inflammatory cell recruitment to the already inflamed joint. In contrast, during the development of active adjuvant arthritis, blockade of P-selectin beginning at day 5 post-immunization had no effect on subsequent arthritis. However, E-selectin blockade at this stage reduced arthritic scores by 70% (P < 0.01) and combined E-selectin plus VLA-4 blockade prevented development of arthritis. Either treatment nearly abolished neutrophil and monocyte recruitment to joints at day 14 and prevented cartilage damage. VLA-4 blockade alone was less effective. Adoptive T-cell transfer of adjuvant arthritis to naive rats employed spleen/lymph node lymphocytes from Mycobacterium butyricum immunized rats stimulated with Concanavalin A in vitro (48 h). E-selectin +/- P-selectin blockade had no effect on the development of adoptive arthritis. However, VLA-4 integrin blockade inhibited adoptive arthritis severity by 55% (P < 0.01). LFA-1 blockade had no effect. In adoptive adjuvant arthritis, inhibition of arthritis clinically and by histology was essentially complete (> 90%) when E- and P-selectin blockade was combined with VLA-4 blockade. Thus, in the development of actively induced arthritis E-selectin plays an important role, likely mediating early antigen reactive T-cell recruitment to joints. In contrast, VLA-4 and multiple selectin mechanisms are involved in arthritis induction by ex vivo restimulated arthritogenic T cells. Furthermore, in actively induced adjuvant arthritis, P- and E-selectin and VLA-4 are differently important in the initiation of arthritis, and at the time of fully developed joint inflammation.
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PMID:Differential roles of VLA-4(CD49d/CD29) and LFA-1(CD11a/CD18) integrins and E- and P-selectin during developing and established active or adoptively transferred adjuvant arthritis in the rat. 1296 28

Three-dimensional microlocalization of adhesion molecules, i.e. ICAM-1 (intercellular adhesion molecule), VCAM-1 (vascular adhesion molecule), LFA-1 (lymphocyte function-associated antigen), Mac-1 (macrophage differentiation antigen) and VLA-4 (very late activation antigen), expressed on type-A synoviocyte (macrophage-like cell) and type-B synoviocyte (fibroblast-like cell), were detected by immuno-scanning electron microscopy (SEM) to investigate the immunoreactive microenvironment of the superficial synovial intima in lipopolysaccharide (LPS)-induced arthritis of the mouse knee. Type-B synoviocytes extended rich slender processes from the periphery and constructed a cytoplasmic network, to which ICAM-1 was restricted. VCAM-1 was expressed only in the LPS-stimulated group and was relatively limited to the microvilli of type-B synoviocytes. Type-A synoviocytes were located randomly among the network with a smoother surface and expressed Mac-1 and LFA-1, which were counter-receptors for ICAM-1, and VLA-4 for VCAM-1 on the microvilli or lamellipodia. Three-dimensional microlocalization of adhesion molecules suggests that the network constructed by cytoplasmic processes and microvilli of type-B synoviocytes forms the pathway for the migration or the foothold for the fixation of type-A synoviocytes and takes part in forming an immunoreactive environment in the articular cavity.
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PMID:Three-dimensional expression of adhesion molecules on the superficial synovial intima of LPS-induced arthritis of the mouse knee analyzed by immuno-SEM. 1507 4