Degradation Of Immune Complexes Research Articles

Degradation of aggregates of activated C3 (C3b) by monocytes of patients with rheumatoid arthritis is related to vasculitis

We investigated whether a decreased complement receptor expression or function of monocytes isolated from peripheral blood of 52 patients with rheumatoid arthritis (RA) and rheumatoid vasculitis (RV) could account for the previously observed diminished degradation of immune complexes by monocytes of patients with RA and RV. On average, monocytes from all patients expressed significantly less CR1, and degraded significantly less AC3b when compared with monocytes of healthy controls. In addition, monocytes from RV patients degraded significantly less AC3b when compared with monocytes from patients with RA. The expression of both CR1 and CR3 on monocytes of RV patients was lower compared with RA patients but this difference was only significant for CR3. No differences were found between AC3b degradation and the expression of CR1 and CR3 between patients with active and inactive RA. Using linear discriminant analysis on the variables AC3b, CR1 and CR3, 94% of the patients could be classified correctly as healthy controls, RA or RV, suggesting a true multi-variate relationship between these parameters and patients groups. Our results suggest that the diminished capacity of monocytes from RA patients to degrade AC3b is due partly to a decreased expression of CR1 and CR3.

Fc receptor mediated endocytosis of small soluble immunoglobulin G immune complexes in Kupffer and endothelial cells from rat liver.

Soluble circulating immunoglobulin G immune complexes are mainly eliminated by the liver, predominantly by uptake in the Kupffer cells, but also the liver endothelial cells seem to be of importance. In the present study we have followed the intracellular turnover of immune complexes after Fc(gamma) receptor mediated endocytosis in cultured rat liver endothelial cells and Kupffer cells by means of isopycnic centrifugation, DAB cross-linking and morphological techniques. For the biochemical experiments the antigen, dinitrophenylated bovine serum albumin (BSA), was labeled with radioiodinated tyramine cellobiose that cannot cross biological membranes and therefore traps labeled degradation products at the site of formation. The endocytic pathway followed by immune complexes was compared with that followed by scavenger receptor ligands, such as formaldehyde treated BSA and dinitrophenylated BSA, and the mannose receptor ligand ovalbumin. Both Kupffer cells and liver endothelial cells took up and degraded the immune complexes, but there was a clear delay in the degradation of immune complexes as compared to degradation of ligands taken up via scavenger receptors. The kinetics of the endocytosis of scavenger receptor ligand was unaffected by simultaneous uptake of immune complexes. Experiments using both biochemical and morphological techniques indicated that the delayed degradation was due to a late arrival of the immune complexes at the lysosomes, which partly was explained by retroendocytosis of immune complexes. Electron microscopy studies revealed that the immune complexes were retained in the early endosomes that remained accessible to other endocytic markers such as ovalbumin. In addition, the immune complexes were seen in multivesicular compartments apparently devoid of other endocytic markers. Finally, the immune complexes were degraded in the same lysosomes as the ligands of scavenger receptors. Thus, immune complexes seem to follow an endocytic pathway that is kinetically or maybe morphologically different from that followed by scavenger and mannose receptor ligands.

Enhanced Fc receptor function of monocytes from patients with clinically active systemic lupus erythematosus: binding and degradation of soluble immune complexes in vitro.

The in vitro Fc receptor function of monocytes as measured by using soluble immune complexes (IC) consisting of ovalbumin and 125I-labeled antibody to ovalbumin was examined in serum-free medium. Adherent monocytes were obtained from peripheral blood of 18 patients with systemic lupus erythematosus (SLE; 6 active, 12 inactive) and 13 normal controls. 5 X 10(5) monocytes were incubated with soluble IC containing 20 ng IgG for 16 hr at 4 degrees C, and for 4 hr and 16 hr at 37 degrees C, and then cell-associated and acid-soluble radioactivities were counted. After 16-hr incubation at 4 degrees C, there was no significant difference in the amount of cell-associated IC between monocytes from SLE patients and those from normal controls. After 4 hr incubation at 37 degrees C, monocytes from patients with active SLE bound and phagocytized more IC than those from patients with inactive SLE or from normal controls (P less than 0.01). After 16 hr incubation at 37 degrees C, degradation of soluble IC by monocytes from patients with active SLE greatly increased (P less than 0.003). These findings were discussed in relation to the possible pathophysiologic role of the mononuclear phagocyte system in SLE.