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Concerning the Mechanism of Complement Action

III. Inhibitors of Complement Activity^1,2,

From the Division of Immunology, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington 12, D. C.

Abstract

The hypothesis has been advanced that several or all of the components of complement are proteolytic enzymes. It was further proposed that simple chemical substances related to the natural substrates of these supposed enzymes might competitively inhibit the immune hemolysis reaction. Based on these hypotheses over 60 compounds, amino acids, amino acid esters and peptides were tested for their inhibitory action on complement. Three classes of inhibitory compounds were found, sulfhydryl bearing compounds, (cysteine and thioglycollic acid), derivatives of basic amino acids (lysine ethyl ester, TAMe and canavanine) and peptides containing aromatic amino acids. These findings were considered to have supported the hypotheses, but the necessity for further work was stressed. It was further suggested that one of the components of complement might be a proteolytic enzyme either requiring the presence of aromatic amino acids in its substrate, or whose activity is enhanced by substrates containing such acids.

Footnotes

¹ A portion of this work was reported at the meeting of the American Association of Immunologists at Atlantic City, April 19, 1956.

² Present address, College of Medicine, University of Vermont, Burlington, Vermont.