Failure of Complete in Vivo Inhibition of Cathepsin D to Mitigate the Pulmonary Arthus Reaction

Summary

This is the first demonstration that pepstatin levels following i.p. injection may be reached which are totally inhibitory to cathepsin D contained in the lung. Thus an animal model has been created, which is devoid of cathepsin D as demonstrated by measurement of an extract of the lung. When this model was challenged with the pulmonary Arthus reaction no inhibition of the Arthus reaction was observed. We conclude that cathepsin D is not the primary direct mediator of the pulmonary Arthus reaction.

The authors are grateful for the helpful assistance of Drs. P. A. Ward and H. Scherzer of the University of Connecticut School of Medicine and Drs. M. Osman and D. Ischii of Columbia College of Physicians and Surgeons, New York, New York. This project was supported by USPHS Grant HL15832, N.Y. Lung Association Fellowship 538, The Stony Wold-Herbert Fund, and the Council for Tobacco Research.