Pathogenetic mechanisms in the Mycoplasma arthritidis polyarthritis of rats

Abstract

Mycoplasma arthritidis is the causative agent of severe polyarthritis in rats and mice, which resembles human rheumatoid arthritis (RA). Several mechanisms are involved in this disease. M. arthritidis releases substances acting on polymorphonuclear granulocytes (PMNs), i.e. oxygen radical formation stimulating substances (500-3,000 daltons), a chemotactic substance (400 daltons) and an aggregating substance (500 daltons). These products were separated from the cell-free culture supernatant by gel chromatography on Sephadex G-15 and G-10 columns. Isolated membranes of M. arthritidis possesses toxic properties for rats, mice, and chicken embryos. Hemolytic activities for sheep red blood cells and toxic effects on fetal rat skin fibroblasts were detected for this 170,000 dalton substance. Cross-reactivity between M. arthritidis and rat tissues was demonstrated in several investigations with polyclonal and monoclonal antibodies. Polyclonal antibodies against M. arthritidis showed a strong reaction in immunofluorescence tests with rat chondrocytes. In Western blot analysis six corresponding protein bands were observed in M. arthritidis membranes and rat chondrocytes, favoring the idea of several shared epitopes. Monoclonal antibodies were established reacting with M. arthritidis as well as with rat and human chondrocytes in the immunofluorescence test and in the enzyme immunoassay. Cross-reactivity could be observed also on the cellular level. T-cell lines of the OX 19 and W 3/25 type were established that could be stimulated by M. arthritidis antigens and by syngeneic chondrocytes. In the initial stage of the arthritis, toxic processes seem to be predominant that are continued by autoimmune reactions in the progressing disease.