PMC:17821 / 33345-36365 JSONTXT

{"project":"2_test","denotations":[{"id":"11056679-4111070-4381695","span":{"begin":152,"end":154},"obj":"4111070"}],"text":"Expression of FcγRII/III is elevated in resident macrophages of naïve CIA-sensitive mice that are hypersensitive to immune complexes\nIn a recent study [36], we noticed that certain mouse strains that are prone to develop collagen-type-II autoimmune arthritis are also particularly susceptible to immune-complex-induced inflammation. Induction of ICA in the DBA/1 knee joint resulted in a more severe arthritis than that in C57BL/6 mice, and this became chronic (Table 1). Local production of IL-1 was also significantly higher and more prolonged than in C57BL/6 mice, both at 6 and 24 h after ICA induction (Table 2). To investigate whether the enhanced inflammation in DBA/1 mice during ICA was still mediated by FcRs, FcR γ-chain-/- mice were backcrossed to DBA/1 (DBAγ-/-) mice. ICA was induced in these mice and the inflammation was compared with that in DBAγ+/+ littermates. We found that at day 3 after arthritis induction, arthritis was full-blown in DBAγ+/+mice (arbitrary scores of 1.0 ± 0.4 for exudate and 1.6 ± 0.3 for infiltrate) but was completely absent in γ-chain-deficient DBA/1 mice (0.1 ± 0.2 and 0.1 ± 0.1, respectively; not shown).\nTo examine whether the different reactions in knee joints of C57BL/6 and DBA/1 mice to immune complexes might be due to variable local expression of FcγR, expression in situ of FcγRs in naïve knee joints was determined immunohistochemically, using the monoclonal antibody (mAb) 2.4G2 (FcγRII/III). Synovial macrophage-like type A lining cells and deeper-lying synovial macrophages were the dominant cell types expressing these receptors, as was seen in double-labeling studies with F4/80 (data not shown). Interestingly, synovial macrophages of naïve DBA/1 mice stained more intensely than those of C57BL/6 mice (Fig. 3), indicating a higher constitutive expression of FcγRs in lining macrophages of these autoimmune-prone mice.\nTo quantify the difference in FcγR expression by macrophages of the two strains (DBA/1 and C57BL/6), we further investigated receptor expression on peritoneal macrophages, using FACS analysis. Macrophages of DBA/1 mice (mean fluorescence 440 ± 50 intensity per cell) displayed almost twice the mean fluorescence with mAb 2.4G2 as those of C57BL/6 mice (240 ± 30 intensity per cell) (Fig. 4). These findings also indicate that FcγRII/III is significantly upregulated on the membrane of macrophage populations present in various body compartments of naïve DBA/1 mice.\nTo further investigate whether a higher basal FcγR expression on macrophages has consequences for the activation of cells upon interaction with immune complexes, peritoneal macrophages of both strains were incubated with aggregated IgG and production of IL-1 was determined by bioassay. Incubation of C57BL/6 cells for 24 or 48 h caused the release of considerable amounts of bioactive IL-1 (45 pg/ml at 24 h and 50 pg/ml at 48 h) (Fig. 5). Interestingly, DBA/1 macrophages produced significantly higher amounts of IL-1 (120 and 135 pg/ml, respectively) than C57BL/6 mice."}

{"project":"Colil","denotations":[{"id":"T46","span":{"begin":152,"end":154},"obj":"4111070"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/docs/sourcedb/PubMed/sourceid/"}],"text":"Expression of FcγRII/III is elevated in resident macrophages of naïve CIA-sensitive mice that are hypersensitive to immune complexes\nIn a recent study [36], we noticed that certain mouse strains that are prone to develop collagen-type-II autoimmune arthritis are also particularly susceptible to immune-complex-induced inflammation. Induction of ICA in the DBA/1 knee joint resulted in a more severe arthritis than that in C57BL/6 mice, and this became chronic (Table 1). Local production of IL-1 was also significantly higher and more prolonged than in C57BL/6 mice, both at 6 and 24 h after ICA induction (Table 2). To investigate whether the enhanced inflammation in DBA/1 mice during ICA was still mediated by FcRs, FcR γ-chain-/- mice were backcrossed to DBA/1 (DBAγ-/-) mice. ICA was induced in these mice and the inflammation was compared with that in DBAγ+/+ littermates. We found that at day 3 after arthritis induction, arthritis was full-blown in DBAγ+/+mice (arbitrary scores of 1.0 ± 0.4 for exudate and 1.6 ± 0.3 for infiltrate) but was completely absent in γ-chain-deficient DBA/1 mice (0.1 ± 0.2 and 0.1 ± 0.1, respectively; not shown).\nTo examine whether the different reactions in knee joints of C57BL/6 and DBA/1 mice to immune complexes might be due to variable local expression of FcγR, expression in situ of FcγRs in naïve knee joints was determined immunohistochemically, using the monoclonal antibody (mAb) 2.4G2 (FcγRII/III). Synovial macrophage-like type A lining cells and deeper-lying synovial macrophages were the dominant cell types expressing these receptors, as was seen in double-labeling studies with F4/80 (data not shown). Interestingly, synovial macrophages of naïve DBA/1 mice stained more intensely than those of C57BL/6 mice (Fig. 3), indicating a higher constitutive expression of FcγRs in lining macrophages of these autoimmune-prone mice.\nTo quantify the difference in FcγR expression by macrophages of the two strains (DBA/1 and C57BL/6), we further investigated receptor expression on peritoneal macrophages, using FACS analysis. Macrophages of DBA/1 mice (mean fluorescence 440 ± 50 intensity per cell) displayed almost twice the mean fluorescence with mAb 2.4G2 as those of C57BL/6 mice (240 ± 30 intensity per cell) (Fig. 4). These findings also indicate that FcγRII/III is significantly upregulated on the membrane of macrophage populations present in various body compartments of naïve DBA/1 mice.\nTo further investigate whether a higher basal FcγR expression on macrophages has consequences for the activation of cells upon interaction with immune complexes, peritoneal macrophages of both strains were incubated with aggregated IgG and production of IL-1 was determined by bioassay. Incubation of C57BL/6 cells for 24 or 48 h caused the release of considerable amounts of bioactive IL-1 (45 pg/ml at 24 h and 50 pg/ml at 48 h) (Fig. 5). Interestingly, DBA/1 macrophages produced significantly higher amounts of IL-1 (120 and 135 pg/ml, respectively) than C57BL/6 mice."}