Local and systemic complement activity in small intestinal bacterial overgrowth.

It is unknown whether bacteriolysis due to luminal complement activation contributes to local defense mechanisms against small intestinal bacterial overgrowth, particularly with gram-negative bacteria. This study addressed this issue. Thirty adult subjects were investigated with culture of luminal secretions adherent to proximal small intestinal mucosa. Luminal and plasma concentrations of C3 and C3d and C3d/C3 ratios were determined. Activated terminal complement complex was sought in surface epithelium to which aspirated secretions had been adherent. Small intestinal bacterial overgrowth with gram-negative bacteria was present in 12/30 (40.0%) subjects. C3, C3d, and C3d/C3 profile indicated that increased local but not systemic C3 activation occurs in this group. Conversely, no activation of terminal complement complex was evident in this circumstance. Thus, complement-mediated bacteriolysis is unlike to contribute to local defense mechanisms against small intestinal bacterial overgrowth, even when overgrowth flora includes gram-negative bacteria. Factors preventing full local activation of the complement cascade in this circumstance require investigation.

The expression of complement protein 4 and IgG3 in luminal secretions.

BACKGROUND: Factors regulating proximal small-intestinal luminal concentrations of IgG3, the predominant IgG subclass at this site, are unclear. This study determined whether luminal IgG3 concentrations are related to those of complement protein 4 (C4), an acute-phase reactant predominantly derived from local mucosa. METHODS: Proximal small-intestinal luminal and peripheral blood IgG subclass and C4 concentrations were measured by radial immunodiffusion in 30 adult subjects without predisposition to disturbed mucosal immunity. Mucosal C4 immunoreactivity and the presence or absence of small-intestinal bacterial overgrowth were determined in all subjects. Caecal luminal concentrations of IgG3 and C4 were measured in a separate cohort of eight asymptomatic subjects. RESULTS: Proximal small-intestinal luminal C4 and IgG subclass concentrations were not significantly influenced by the presence of absence of small-intestinal bacterial overgrowth (P > 0.2). Nor did plasma C4 levels significantly influence C4 concentrations in small-intestinal luminal secretions (P > 0.2). Mucosal immunoreactivity for C4 was present in every subject. A significant correlation was found between C4 and IgG3 concentrations in proximal small-intestinal luminal secretions (P < 0.0005) and also in caecal secretions (P < 0.05) but not in peripheral blood (P > 0.1). CONCLUSIONS: Common factors, not including the presence or absence of small-intestinal bacterial overgrowth, regulate luminal concentrations of C4 and IgG3. Local investigation is mandatory when assessing mucosal immune mechanisms.

Proliferative glomerulonephritis in mice induced by sea snake (Aipysurus laevis) venom.

Aipysurus laevis venom has been shown to have a direct nephrotoxic effect in mice. A single subcutaneous injection (0.075 mg/kg body wt.) of the whole venom caused acute renal tubular degeneration and proliferative glomerulonephritis. The tubular changes appeared within 1 hour and remained for at least 14 days. Mesangial proliferative glomerulonephritis developed within 3-10 days, and is characterised by mild mesangial proliferation, mesangial and glomerular basement membrane deposits. This is followed by a partial resolution and subsequent mesangial sclerosis. The exact pathogenesis of venom-induced glomerulonephritis is not clear although it may have an immunological basis similar to that seen in human poststreptococcal glomerulonephritis. It was not possible to clarify the nature of the deposits by conventional immunohistochemical stains.