The effect of a low molecular weight inhibitor of lipid peroxidation on ultrastructural alterations to ischemia-reperfusion in the isolated rat heart

The effects of H290/51, a novel indenoindole derivative inhibitor of lipid peroxidation, on ultrastructural changes during cardiac ischemia-reperfusion injury were investigated. Langendorff-perfused rat hearts were exposed to 30 minutes of global ischemia followed by 20 minutes of reperfusion: Group A: Control hearts with standard buffer perfusion with vehicle added. Group B: H290/51 (10-6 mol/l) added to buffer throughout stabilisation and reperfusion. In an additional Group C, where hearts were given H290/51, but not subjected to ischemia, the ultrastructure was preserved till the end of reperfusion. Absolute volumes and calculated volume fractions (Vv) of tissue and subcellular components were assessed with quantitative stereologic morphometry. After ischemia the increase in volume of extracellular interstitium was inhibited by H290/51 (247±80 vs. 159±50ml, mean±SD, groups A and B, respectively, p<0.05). The Vv (interstitium/myocard) was higher in control hearts (0.318±0.062 vs. 0.206±0.067, p<0.05). Vv (cell edema/myocyte) was higher in the control group (0.144±0.07 vs. 0.083±0.033, p<0.05). Vv (myocyte/myocard) was higher in group B after ischemia than in the control group (0.622±0.071 vs. 0.707±0.052, p<0.05). The decreased Vv (capillary/myocard) after ischemia was inhibited by H290/51. After reperfusion there was no difference between groups. Treatment with H290/51 reduced edema and ensured better preserved sarcolemmal membrane structure during ischemia. The effect was no longer present after reperfusion.

Effect of protein A of Staphylococcus aureus on the binding of monomeric and polymeric IgG to Fc receptor-bearing cells.

The effect of protein A of Staphylococcus aureus (SpA) on the binding of rabbit IgG to the Fc receptors of mouse lymphocytes and macrophages was found to correlate with the aggregation of the IgG ligands. After binding anti-erythrocyte IgG complexed with SpA, the cells were able to attach to and kill erythrocyte indicator cells with a higher efficiency than lymphoid cells treated with anti-erythrocyte IgG alone. The amount of anti-peroxidase IgG which can be bound to effector cells was not changed by reaction with SpA. In contrast, the binding to cells of IgG-coated erythrocytes and of anti-peroxidase IgG complexed with peroxidase was substantially reduced by reaction with SpA. The results are compatible with the presence of two distinct Fc receptors, one for cytophilic monomeric IgG and another for polymeric (antigen-complexed) IgG

Herpes simplex type 1-induced Fc receptor binds to the Cgamma2-Cgamma3 interface region of IgG in the area that binds staphylococcal protein A

The binding site of immunoglobulin G (IgG) to herpes simplex virus (HSV) type 1-induced Fc receptor was investigated using human IgG Fc intermediate (Fc(i)) fragments, fragment D of staphylococcal protein A (SPA) and chemically modified human IgG. Human IgG Fc(i) fragment composed of one Cgamma2 and two Cgamma3 domains, bound strongly to HSV-1-infected cells. Fragment D, a monovalent subunit of SPA, inhibited the binding of radiolabelled human IgG Fc fragments to the HSV Fc receptor. Reductively methylated human IgG reacted equally well to HSV-infected cells, as did chemically unmodified IgG in contrast to N-acetylimidazole-modified and diethylpyrocarbonate-modifed human IgG, which were unreactive. These results suggest a similar binding site on human IgG for SPA and the HSV-1 Fc receptor with involvement of the amino acid residues Tyr and His but not Lys. The similarities of binding sites on the IgG molecule for the HSV-1 Fc receptor and rheumatoid factors (RF) may be important for understanding the mechanism of RF production in rheumatoid arthritis or other disease states