The effect of protease inhibitors on the polyclonal B cell activator from the serum of patients with rheumatoid arthritis.
It has been reported that polyclonal B cell stimulation results in formation of autoantibodies and immune complexes. We have previously reported that a polyclonal B cell activator (PBA) associated with alpha 2-macroglobulin (alpha 2M) is present in the serum of patients with rheumatoid arthritis and related diseases. Here we studied the possibility that patient alpha 2M (Pt-alpha 2M) carries a trypsin-like protease responsible for the PBA activity. This activity was determined by the Ig-turnover assay developed in our laboratories. The small molecular weight protease inhibitors, aprotinin (Trasylol, Bayer) and phenylmethylsulfonylfluoride (PMSF), and the large molecular weight soybean trypsin inhibitor (SBTI) were used. These inhibitors did not affect the PBA activity of dextran sulfate of LPS. However, as expected, trypsin had a PBA-activity which was blocked by all of the above mentioned inhibitors. A trypsin-normal alpha 2M complex (Tr-N alpha 2M) and PBA activity which was inhibited by PMSF or aprotinin but not by SBTI. The PBA associated with Pt-alpha 2M was also inhibited by PMSF or aprotinin but not by SBTI. Moreover, the Tr-N alpha 2M complex and the Pt-alpha 2M, but not that from normal donors, had esterase activity for p-toluenesulfonyl-L-argininemethyl ester. These data suggest a similarity between the Pt-alpha 2M and Tr-N alpha 2M complex. Thus, we concluded that the esterolytic activity is sufficient for PBA activity, that Pt-alpha 2M has esterolytic activity and that this PBA activity can be blocked by small molecular weight protease inhibitors.
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood*; D002457:Cell Extracts / Q000494:pharmacology*; D004950:Esterases / Q000037:antagonists & inhibitors; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D015847:Interleukin-4; D011480:Protease Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D014020:Tissue Extracts / Q000494:pharmacology*; D014357:Trypsin / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000494:pharmacology
D002457:Cell Extracts; D007136:Immunoglobulins; D011480:Protease Inhibitors; D014020:Tissue Extracts; D000511:alpha-Macroglobulins; D015847:Interleukin-4; D004950:Esterases; D014357:Trypsin