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Notes: Slices from the guinea-pig olfactory cortex were incubated in the medium containing [14C]glutamate and release of radioactive compounds was subsequently studied in the standard or high potassium media or during repetitive stimulation of the lateral olfactory tract (LOT) while electrical activity of the tissue was monitored. In 50 mm-potassium concentration, the pre- and postsynaptic potentials were completely suppressed and effluxes of total 14C and [14C]glutamate increased. No significant increase in [14C]glutamine was found. When Ca2+ concentration was reduced from 2·4 to 0·12 mm, the postsynaptic potential disappeared and release of [14C]glutamate in 50 mm-potassium decreased to about a third of that in 2·4 mm-Ca2+. Repetitive LOT stimulation enhanced release of total 14C in thinner slices but caused no significant increase in [14C]glutamate efflux. These findings were discussed in relation to the possibility that glutamate is a mediator between the LOT fibres and cortical neurons.

Notes: Abstract— Thin sections prepared from the olfactory cortex of the guinea pig were incubated in a medium containing [14C]glutamate, and release of radioactive compounds and electrical activity were subsequently examined in the presence of l-cysteate. The postsynaptic potential was almost completely suppressed in the medium containing l-cysteate, whereas the presynaptic potential was unaffected. Repetitive stimulation of the excitatory input of the lateral olfactory tract enhanced release of radioactive glutamate. The facilitatory effect of lateral olfactory tract stimulation increased with increase in stimulus frequency and was dependent on calcium. Release of radioactive gluiamine was not enhanced by lateral olfactory tract stimulation. Phenobarbitone sodium markedly depressed both the postsynaptic potential and the effect of lateral olfactory tract stimulation on glutamate release. These results indicate that stimulation to the lateral olfactory tract enhances liberation of glutamate from the tract nerve terminals.

Notes: IgA nephropathy (IgAN) is characterized by the presence of IgA deposits, predominantly in the glomerular mesangium, and by mesangial proliferative glomerulonephritis (GN). Concerning its pathogenesis, several investigators have suggested that the glomerular IgA deposits in IgAN are antibodies (Ab) to viral, bacterial or dietary antigens. Thus, the Ab are probably produced as part of the specific host immune response to various environmental antigens. Such reports strengthen the possibility of a relationship between mucosal immunity and the pathogenesis of IgAN. Nevertheless, attempts to isolate a specific IgA circulating immune complex-associated antigen in patients with IgAN have been unsuccessful.We have shown that mucosal infections such as pharyngitis are often associated with the acute onset of IgAN.1 IgAN is, then, an immune complex disease that is caused by a poor mucosal immune response to environmental antigens to which the patient has been chronically exposed. We have observed previously that Haemophilus parainfluenzae (HP) is more commonly isolated from the pharynx of patients with IgAN than from those with other glomerular diseases.2 We have also identified the glomerular deposition of outer membranes of HP antigens (OMHP) and an increased serum concentration of IgA-Ab against OMHP in patients with IgAN.2 Furthermore, we have shown that patients with IgAN have a specific increase in the production of IgA-Ab against OMHP via polyclonal activation against these, with switching of production from one isotype to another (e.g. from IgM to IgA3), and that a significant relationship between IgA-Ab against OMHP and renal lesions exists in patients with IgAN,4 and that OMHP stimulate tonsillar B-lymphocytes to produce specific IgA1-Ab against OMHP and tonsillar T-lymphocytes in patients with IgAN.5,6Our objective was to investigate the production of IgA and several cytokines by tonsillar lymphocytes from patients with IgAN induced by stimulation with OMHP. We used tonsillar lymphocytes from the palatine tonsils of 18 patients with IgAN and 25 patients with chronic tonsillitis but without renal diseases as controls. There were no significant differences in the backgrounds of the two groups. Haemophilus parainfluenzae was detected in the tonsils of all 43 patients before tonsillectomy. We examined production of total IgA, IgA-Ab against OMHP, IL-4, IL-6, IL-10, and TGF-β in the culture supernatants after lymphocyte incubation with OMHP. The spontaneous production of total IgA and TGF-β by tonsillar lymphocytes from patients with IgAN was higher than that by tonsillar lymphocytes from controls (P 〈 0.05). Stimulation with OMHP in vitro enhanced the production of HP-specific IgA by tonsillar lymphocytes from patients with IgAN (P 〈 0.01), but not by tonsillar lymphocytes from controls. Outer membranes of HP stimulation also enhanced the production of TGF-β and IL-10 by tonsillar lymphocytes from patients with IgAN (P 〈 0.001).Our results suggest that the infection of HP in the tonsil may be involved in the aetiology of IgAN.

Notes: IgA nephropathy (IgAN) was first reported by Berger in 1968, and characterized by diffuse IgA deposits in glomerular mesangium and mesangial proliferative glomerulonephritis. Clinically, patients with IgAN have frequently episodic macroscopic haematuria accompanied with pharyngitis, tonsillitis, gastroenteritis, bronchitis, or sinusitis. These findings suggest that IgAN is related to inflammatory and immune responses to mucosal infections.We have reported that primary IgAN patients with acute onset are often associated with mucosal infections such as pharyngitis and tonsillitis, and Haemophilus parainfluenzae (HP) is more frequently isolated from the pharynx of patients with IgAN than from those with other diseases.1 We also demonstrated glomerular deposition of outer membrane of HP (OMHP) antigens and the presence of IgA antibody against OMHP in patients with IgAN.1 These findings suggest that HP has a role in the aetiology of primary IgAN.In the present study, we attempt to develop an experimental model of IgAN induced by oral and intraperitoneal immunization of OMHP antigens, and evaluate the difference in immunological and histopathological changes between these two administration routes.Four-week-old female C3H/HeN mice were fed mouse chow. One hundred and twenty mice were divided into oral (PO group) and intraperitoneal (IP group) administration groups of OMHP antigens and each control groups. Mice of the PO group received OMHP antigens for daily drinking water and intragastric intubation once a week, and mice in the IP group received intraperitoneal injection of 0.1 mL of OMHP antigens, once a week. Six mice from each group were killed at 10, 20, 30, 40 and 50 weeks of age to examine sequential glomerular changes. We also measured serum IgG, IgA, IgM antibody against OMHP antigens, and serum IL-10 and IFN γ by ELISA. Throughout experiments, haematuria and proteinuria were analysed every 5 weeks.IgA antibodies against OMHP significantly increased in PO and IP groups compared with the control, and the degree of increase in IgA antibodies against OMHP was more prominent in the PO group. In the IP group, IgG and IgM antibodies against OMHP increased more markedly. Glomerular deposition of IgA and increase of mesangial matrix were observed in the PO group from 40 weeks of age and in the IP group from 30 weeks of age, respectively. Mice in both groups showed glomerular deposition of OMHP antigens. Haematuria was not detected in any group. Serum IL-10 tended to increase in the PO and IP groups, and IFN γ did not increase significantly in any group.These results suggest that oral administarion of OMHP antigens induce glomerular deposition of IgA and mesangial proliferation with increase of IgA antibodies against OMHP antigens in mice, and these observations in the PO group resemble the changes of human IgAN more closely than in the IP group.