Immune complex processing in C1q-deficient mice - PubMed (original) (raw)
Immune complex processing in C1q-deficient mice
J T Nash et al. Clin Exp Immunol. 2001 Feb.
Abstract
Complement and Fcgamma receptors are known to mediate the processing of immune complexes (IC), and abnormalities in these mechanisms may predispose to the development of lupus. We explored the processing of IC in mice deficient in complement component C1q. 125I-labelled IC comprising Hepatitis B surface antigen (HBsAg)/human anti-HBsAg (HBsAg/Ab) were injected intravenously and the sites of IC clearance determined by direct counting of organ uptake at various time points. The liver and spleen were the main sites of IC uptake in all mice. The splenic uptake of IC was significantly reduced in the C1q-deficient mice compared with the control mice. C1q-deficient mice also exhibited an initial accelerated hepatic uptake of IC similar to that seen in human subjects with hypocomplementaemia. The hepatic localization of IC at later time points was similar in both groups of mice. These data in mice are consistent with previous observations in humans that confirm that the classical pathway of complement plays an important role in the appropriate processing of IC in vivo.
Figures
Fig. 1
Fixation of murine complement by HBsAg/Ab IC. Graph demonstrating binding of the opsonized HBsAg/Ab IC to the solid phase ligand (polyclonal antimouse C3) via C3b. There is negligible binding of the HBsAg/Ab IC when treated with heat inactivated normal mouse serum (HINMS) or PBS rather than normal mouse serum (NMS). HbSAg alone treated with NMS does not bind significantly. This demonstrates that only the HBsAg/Ab IC was able to fix complement in the form of C3b.
Fig. 2
Kinetics of HBsAg/Ab IC processing in C1q-deficient mice. Graphs showing the kinetics of organ uptake of HBsAg/Ab IC, expressed as percentage of injected radioactivity, in C1qa -/– (○) and C1qa+/+ (•) mice. (a) The splenic uptake of IC was significantly reduced in the C1qa -/–mice by five minutes after injection and remained so throughout the time course. (b) The hepatic uptake of IC was initially accelerated (at 10 s) in the C1q-deficient mice but became not detectably different from the wild‐type controls at the following time points. (c) The lung showed an increased uptake of IC during the first 10 min in the C1qa+/+ mice compared with the C1qa -/–mice. Data are expressed as means ± standard error of the mean. *P < 0·05, **P < 0·01, ***P < 0·001
Fig. 3
Kinetics of clearance of HBsAg/Ab IC from the bloodstream of C1qa -/– (○) and C1qa+/+ (•) demonstrating no significant difference in the clearance of the IC from the blood between the C1q-deficient mice and their wild type controls.
Fig. 4
HBsAg/Ab IC organ retention. Splenic and hepatic uptake and retention of HBsAg/Ab IC at 2 and 15 h in C1qa -/–(○) and C1qa+/+(•) mice. Horizontal bars denote means. (a) A highly significant reduction in the splenic uptake of IC in the C1q-deficient mice compared with the controls was observed at both 2 and 15 h postinjection (P < 0·0001 for both time-points). (b) No difference was found in the liver at these times.
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