TRYPTASE CLARA, AN ACTIVATING PROTEASE FOR SENDAI VIRUS IN RAT LUNGS, IS INVOLVED IN PNEUMOPATHOGENICITY

Tryptase Clara is an arginine-specific serine protease localized exclusively in and secreted from Clara cells of the bronchial epithelium of rats (H. Kido, Y. Yokogoshi, K. Sakai, M. Tashiro, Y. Kishino, A. Fukutomi, and N. Katunuma, J. Biol. Chem. 267:13573-13579, 1992). The purified protease was shown in vitro to behave similarly to trypsin, cleaving the precursor glycoprotein F of Sendai virus at residue Arg-116 and activating viral infectivity in a dose-dependent manner. Anti-tryptase Clara antibody inhibited viral activation by the protease in vitro in lung block cultures and in vivo in infected rats. When the enzyme-specific antibody was administered intranasally to rats that were also infected intranasally with Sendai virus, activation of progeny virus in the lungs was significantly inhibited. Thus, multiple cycles of viral replication were suppressed, resulting in a reduction in lung lesions and in the mortality rate. These findings indicate that tryptase Clara is an activating protease for Sendai virus in rat lungs and is therefore involved in pulmonary pathogenicity of the virus in rats.