Comparative nephritogenicity of two monoclonal antibodies that recognize different epitopes of rat Thy-1.1 molecule.

摘要

The pathophysiological role of the Thy-1.1 molecule expressed on rat mesangial cells with regard to mesangial cell dysfunction and injury remains unknown. The mechanism of Thy-1.1-associated injury has now been investigated with two monoclonal antibodies, 1-22-3 and OX7, that recognize different epitopes of Thy-1.1. Mesangiolysis and mesangial cell proliferation were more marked in rats injected with 1-22-3 than in those treated with OX7. Immunostaining for rat complement component C3 and also C9 was similar in the kidneys of rats 1 h after injection of either antibody. Alpha smooth muscle actin was first detected 3 days after injection of 1-22-3 and peaked on day 5; type I collagen staining showed a mesangial pattern on days 5 and 10. The staining for alpha smooth muscle actin and type I collagen was less intense in OX7-treated rats than in the 1-22-3-injected rats. The amounts of mRNAs encoding collagen types I and III peaked 5 days after injection of 1-22-3 and 10 days after injection of OX7. Rats injected with 1-22-3 developed proteinuria that was already marked on day 1 and peaked at 150 mg/day on day 3, whereas OX7 induced a low grade of proteinuria with large interindividual variability on day 3. Immunostaining for rat C3 in the normal rat kidneys, incubated in vitro with 1-22-3 or OX7 followed by incubation with normal rat fresh serum as a complement source, as well as the levels of serum complement activity, CH50, 30 min after injection of 1-22-3 or OX7 were similar, suggesting that the difference in the nephritogenicity of these two antibodies is not attributable to a difference in their complement-fixing activities, but rather may result from the difference in epitope specificities. The epitope recognized by 1-22-3 thus appears to be important in the initiation and progression of antibody-induced nephritis.