Receptors for immunoglobulin (Ig)G (FcγRs) are important the antibody-mediated effector functions of immune system. FcγRI and FcγRIII trigger cell activation through a common γ chain, whereas FcγRII acts as negative regulator antibody production complex–triggered activation. Here we describe in vivo consequences FcγR deficiency mouse model human rheumatoid arthritis. FcRγ chain–deficient mice on arthritis-susceptible DBA/1 background were immunized with collagen induction collagen-induced...

Abstract Collagen-induced arthritis (CIA) is an experimental animal model of human rheumatoid being characterized by synovitis and progressive destruction cartilage bone. CIA induced injection heterologous or homologous collagen type II in a susceptible murine strain. DBA/1J mice deficient complement factors C3 (C3−/−) factor B (FB−/−) were generated to elucidate the role system CIA. When immunized with bovine emulsified CFA, control developed severe high CII-specific IgG Ab titers. In...

Abstract Arthritis was induced in Lewis and DA rat strains after immunization with native homologous type II collagen (CII). Differences were noted the clinical signs of arthritis 2 strains, which immunized same arthritogenic preparation CII. rats showed disease onset characterized by symmetric involvement interphalangeal joints hind feet. only ankle or knee joints. Moreover, tended to be chronic (i.e., persistent variable redness swelling seen joints) rats, but not rats. Analysis...

IgG anti-collagen type II (CII) antibodies (Ab) can induce arthritis in healthy mice. Here we have investigated if single monoclonal anti-CII Ab CIA-susceptible DBA/1 mice and there is an subclass dependency. The involvement of Fc receptors for (FcgammaR) Ab-mediated was also by comparing the clinical outcome to those FcgammaR-deficient We demonstrate first time that mAb naive persistent arthritis. Histology inflamed joints revealed massive cellular infiltrate cartilage bone destruction. All...

Circulating immune complexes are implicated in the pathogenesis of rheumatic disorders and interaction these with IgG Fc receptors (FcγR) seems to be a determining step initiation inflammatory process. Mice deficient FcRγ-chain, thus lacking multiple FcR, have previously been shown protected from collagen-induced arthritis (CIA). However, relative contribution different FcγR has not identified. In this study, we investigated expression FcγRIII, activating low-affinity development CIA....

Multiple sclerosis (MS) is simulated by various forms of experimental autoimmune encephalomyelitis, in which T cells, antibodies, cytokines and complementary factors interact with the central nervous system (CNS) myelin proteins lead to inflammatory damage. We investigated role Fc receptors (FcRs), link cellular humoral branches immune system, oligodendrocyte glycoprotein (MOG)‐induced encephalomyelitis (EAE), using two different FcRγ knockout DBA/1 mice. The first were chain‐deficient mice,...

The cumulative incidence of rheumatoid arthritis (RA) was compared between different occupations, and exposure groups based on a job-exposure matrix (JEM). study population comprised those subjects who in 1980 lived one 13 Swedish counties, were born 1905 1945, had stated the same occupation censuses 1960 1970, total 375,035 men 140,139 women. followed concerning hospital care for 1981-1983 by lineage to Hospital Discharge Register. In general there rather small differences relative risk RA...

Mast cells are implicated in rheumatoid arthritis, but the mechanism by which they contribute to disease progression is not clarified. Here we investigated whether mouse mast cell protease-4 (mMCP-4), a chymase present secretory granule, contributes experimental arthritis. Two models of arthritis were mMCP-4+/+ and mMCP-4−/− DBA/1 mice: collagen-induced (CIA) was induced immunization with collagen II (CII) Freund's complete adjuvant, passive model administration anti-CII antibodies. The...

In this study we wanted to gain insights into selectivity mechanisms between G-protein-coupled receptors (GPCR) and different subtypes of G-proteins. The thyrotropin receptor (TSHR) binds G-proteins promiscuously activates both Gs (cAMP) Gq (IP). Our goal was dissect patterns for pathways in the intracellular region receptor. We were particularly interested participation poorly investigated parts. systematically amino acids loop (ICL) 1 helix 8 using site-directed mutagenesis alongside...

Experimental arthritis can be induced in the DA rat strain with type II collagen (RCII) administered Freund's incomplete adjuvant oil (FIA) or only FIA. If ovalbumin (Ova), is added to these arthritogens development of blocked. To investigate mechanisms responsible for induction arthritis, as well inhibition a kinetic study local cytokine expression lymph nodes has been performed after immunization above mentioned agents. By using situ hybridization techniques, mRNA TNF-alpha, IL-2,...

Monocytes were previously thought to be the precursors of all tissue macrophages but have recently been found represent a unique population cells, distinct from majority macrophages. and intestinal seem now only monocyte/macrophage populations that originate primarily adult bone marrow. To obtain better view biological function monocytes how they differ macrophages, we performed quantitative analysis its transcriptome in vivo after vitro stimulation with E. coli LPS. The rapidly responded...

The serum hyaluronate (HA) concentration was measured in groups of rats immunized for adjuvant or type II collagen arthritis. Serum HA increased as the arthritic lesions developed, correlating with severity disease. This increase not related to metabolic impairment, because arthritis metabolized intravenously administered tritiated at a rate similar that normal rats. levels may be useful an indicator synovitis experimental and possibly clinical Further, this model could serve approach...

Activating Fc gamma receptors (FcgammaRs) have been identified as having important roles in the inflammatory joint reaction rheumatoid arthritis (RA) and murine models of arthritis. However, role inhibitory FcgammaRIIb regulation synovial inflammation RA is less known. Here we investigated tissue from patients using a novel monoclonal antibody (GB3) specific for isoform. was abundantly expressed synovia patients, sharp contrast to absence or weak staining biopsies healthy volunteers. In...

Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults and significant end-stage renal disease, yet current therapies are nonspecific, toxic, often ineffective. The development novel targeted requires detailed understanding the pathogenic mechanisms, but progress hampered by lack robust mouse model disease. We report that DBA/1 mice as well congenic FcγRIII(-/-) FcRγ(-/-) immunized with fragment α3(IV) collagen developed massive albuminuria syndrome, because...

Goodpasture disease is an autoimmune kidney mediated by autoantibodies against noncollagenous domain 1 (NC1) monomers of α3(IV) collagen that bind to the glomerular basement membrane (GBM), usually causing rapidly progressive glomerulonephritis (GN). We identified a novel type human IgG4-restricted anti-GBM associated with mild nonprogressive GN, which specifically targeted α345NC1 hexamers but not α3NC1 monomers. The mechanisms eliciting these were investigated in mouse models...