ABSTRACT
Deficiency of the inhibitory FcgammaRIIB renders mice susceptible to autoimmune disorders characterized with cellular infiltration of target tissue. To analyze the role of FcgammaRIIB in an antibody-mediated autoimmune disease, experimental autoimmune myasthenia gravis (EAMG), FcgammaRIIB knockout (KO) and wild-type mice were immunized with acetylcholine receptor (AChR). In contrast with previous reports, FcgammaRIIB KO mice were mildly resistant to EAMG despite preserved anti-AChR antibody production and neuromuscular junction complement deposition capacity. EAMG resistance was associated with reduced lymph node cell IL-6 and IL-10 production and increased CD4(+)CD25(+) cell ratios in lymph nodes. Our data suggest that FcgammaRIIB promotes antibody-mediated autoimmunity.
Subject(s)
Autoantibodies/immunology , Immunoglobulin G/immunology , Myasthenia Gravis, Autoimmune, Experimental/immunology , Receptors, IgG/physiology , Animals , Antigen-Antibody Complex/blood , CD4-Positive T-Lymphocytes/immunology , Complement C3/analysis , Complement Membrane Attack Complex/analysis , Cytokines/biosynthesis , Genetic Predisposition to Disease , Germinal Center/immunology , Germinal Center/pathology , Immunoglobulin G/biosynthesis , Immunoglobulin M/biosynthesis , Lymph Nodes/metabolism , Lymphocyte Activation , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptors, Cholinergic/immunology , Receptors, IgG/deficiency , Receptors, IgG/genetics , Spleen/immunology , Spleen/pathology , T-Lymphocyte Subsets/immunologyABSTRACT
AIM: To evaluate the effects of prucalopride on intestinal prokinetic activity in fast rats and to provide experimental basis for clinical treatment of gastrointestinal motility diseases. METHODS: Gastrointestinal propulsion rate was measured by the migration rate of activated charcoal, which reflexes gastrointestinal motility function. 120 Spraque-Dawley rats were randomly divided into four groups and received an intravenous injection of physiological saline (served as control), prucalopride 1 mg/kg, prucalopride 2 mg/kg and cisapride 1 mg/kg, respectively. The gastrointestinal propulsion rate was measured 1, 2 or 4 hours after intravenous injection of the drugs. RESULTS: Significant accelerations of gastrointestinal propulsion rate in prucalopride 1 mg/kg and 2 mg/kg groups were found compared with control group at 2 and 4 hours(83.2 %+/-5.5 %, 81.7 %+/-8.5 % vs 70.5 %+/-9.2 %, P<0.01; 91.2 %+/-2.2 %, 91.3 %+/-3.9 % vs 86.8 %+/-2.6 %, P<0.01). The gastrointestinal propulsion rates at 1, 2 or 4 hours were faster in prucalopride 1 mg/kg and 2 mg/kg groups than in cisapride group (84.0 %+/-11.7 %, 77.1 %+/-11.9 % vs 66.3 %+/-13.6 %, P<0.01, P<0.05; 83.2 %+/-5.5 %, 81.7 %+/- 8.5 % vs 75.4 %+/-5.9 %, P<0.01, P<0.05; 91.2 %+/-2.2 %, 91.3 %+/-3.9 % vs 88.6 %+/-3.5 %,P<0.05, P<0.05). No difference of gastrointestinal propulsion rate was found between prucalopride 1 mg/kg group and prucalopride 2 mg/kg group (P>0.05). CONCLUSION: Prucalopride accelerates intestinal motility in fast rats, and has no dose dependent effect.
