PULMONARY SURFACTANT IS A POTENTIAL ENDOGENOUS INHIBITOR OF PROTEOLYTIC ACTIVATION OF SENDAI VIRUS AND INFLUENZA-A VIRUS

The pathogenicities of influenza viruses and paramyxoviruses have been proposed to be primarily determined by a host cell protease(s) that a ctivates viral infectivity by proteolytic cleavage of the envelope gly coproteins. We recently isolated a trypsin-type endoprotease, named tr yptase Clara, from rat bronchial and bronchiolar epithelial Clara cell s, which is secreted into the airway lumen and activates Sendai virus and influenza A virus proteolytically. We report here that surfactant in the bronchial fluid inhibited tryptase Clara specifically, having a K(i) value of 0.13 muM, and inhibited the proteolytic activations by tryptase Clara in vitro and in organ cultures of rat lung. Intranasal infection of rats with Sendai virus was shown to stimulate secretion o f tryptase Clara without changing the amount of surfactant in the bron chial lumen, resulting in a preferable condition for proteolytic viral activation and multiplication.