Open in a separate window FIG. molecules were related in the three patient organizations. We conclude that certain adhesion molecules, including ICAM-1 and LFA-1, are indicated intensely in the synovia of individuals with Lyme arthritis. Upregulation of LFA-1 on lymphocytes with this lesion may be essential in the pathogenesis of treatment-resistant Lyme arthritis. Lyme disease worldwide is caused by three genospecies of the tick-borne spirochete sensu lato (11). In the United States, where the illness is caused by sensu stricto strains, intermittent or chronic oligoarticular arthritis primarily influencing large bones, especially the knees, is definitely a prominent late manifestation of the illness (33C35). Although most individuals with Lyme arthritis can be treated efficiently with Bethoxazin antibiotic therapy, about 10% of individuals have persistent knee Rabbit Polyclonal to CYSLTR2 swelling for weeks to years after 2 weeks of oral antibiotics or one month of intravenous antibiotics. This condition has been termed antibiotic treatment-resistant Lyme arthritis. Adhesion molecules in inflammatory foci have three important cellular functions: homing to lymphoid cells, migration to inflammatory sites, and costimulation of cellular activation (23). You will find four major structural classes of adhesion molecules (examined by Janeway et al. and McMurray [18, 21]). The selectins and vascular addressins mediate the initial phases of extravasation, which cause the tethering and rolling of leukocytes on endothelial surfaces (31). Leukocyte integrins, including lymphocyte function connected antigen-1 (LFA-1 [L2]) and very late antigen-4 (VLA-4 [41]), bind to their ligands of the immunoglobulin superfamily, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), respectively Bethoxazin (1, 18, 22). These relationships attach leukocytes securely to endothelial surfaces. Binding of these adhesion molecules also mediates intercellular communication in inflammatory foci. For example, the connection of LFA-1 on T cells with its main ligand, ICAM-1, on macrophages anchors the cells collectively and provides a potent costimulatory transmission for T-cell activation (18). In addition to having standard functions, sponsor adhesion molecules seem to have specific effects in the pathogenesis of illness. The spirochete attaches to the platelet-specific integrin receptor (IIb3), also known as the fibrinogen receptor, which is expressed only on activated platelets (9). This mechanism may aid the spirochete in homing to sites of endothelial cell injury. In addition, the spirochete binds the ubiquitous vitronectin (v3) and fibronectin (51) receptors (10) and attaches to various proteoglycans, including decorin, which decorates the surface of collagen (15, 27). Attachment to these adhesion molecules may be crucial in the spread and survival of in the joint. Furthermore, it has recently been proposed that autoimmunity develops within the proinflammatory milieu of the joints in genetically susceptible patients with Lyme arthritis because of molecular mimicry between a dominant T-cell epitope of outer-surface protein A (OspA) of and LFA-1 (14). Thus, the expression of adhesion molecules may have specific pathologic consequences in Lyme arthritis. The histopathological appearance of the synovial lesion in Lyme arthritis, which includes synovial hyperplasia, vascular proliferation, and lymphoid infiltrates, is similar to that seen in other chronic inflammatory arthritides, including rheumatoid arthritis (32). In rheumatoid arthritis, adhesion molecules, including P-selectin, LFA-1, ICAM-1, VLA-4, and VCAM-1, are up-regulated within the intense proinflammatory milieu of the synovial lesion (16, 20, 36). In addition, in the murine model of acute Lyme arthritis, P-selectin, ICAM-1, and VCAM-1 are upregulated in by enzyme-linked immunosorbent assay and Western blotting, interpreted according to the Centers for Disease Control-Association of State and Territorial Public Health Laboratory Directors criteria (6, 7). Their ages ranged from 10 to 66 years (median, 36 years); 15 were female, and 14 were male. The median duration from the onset of Bethoxazin arthritis to synovectomy was 12 months (range, 6 to 96 months). All 29 patients were treated for their arthritis with antibiotic therapy, usually oral doxycycline and intravenous ceftriaxone for 30 Bethoxazin days each. The median elapsed time from antibiotic treatment to synovectomy.
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