Lactoferrin, a potent tryptase inhibitor, abolishes late-phase airway responses in allergic sheep

96Citations
Citations of this article
29Readers
Mendeley users who have this article in their library.
Get full text

Abstract

Tryptase, a serine protease released exclusively from activated mast cells, has been implicated as a potential causative agent in asthma. Enzymatically active tryptase is comprised of four subunits, and heparin stabilizes the associated tetramer. Lactoferrin, a cationic protein released from activated neutrophils, binds tightly to heparin, therefore we investigated lactoferrin as an inhibitor of tryptase and found that it is both a potent (K1 is 24 nM) and selective inhibitor. Size exclusion chromatography studies revealed that lactoferrin disrupted the quaternary structure of active tryptase. Lactoferrin was tested in an allergic sheep model of asthma; aerosolized lactoferrin (10 mg in 3 ml phosphatebuffered saline, 0.5 h before as well as 4 and 24 h after inhalation challenge by Ascaris suum) abolished both late-phase bronchoconstriction (no significant increase in specific lung resistance 4 to 8 h following provocation, p < 0.05 versus vehicle treatment) and airway hyperresponsiveness (no detectable increase in airway sensitivity to carbachol challenge 24 h after antigen challenge, p < 0.05 versus vehicle). These data suggest tryptase involvement in both late-phase bronchoconstriction and airway hyperreactivity and furthermore suggest that a physiological function of neutrophil lactoferrin is the inhibition of tryptase released from mast cells.

Cite

CITATION STYLE

APA

Elrod, K. C., Moore, W. R., Abraham, W. M., & Tanaka, R. D. (1997). Lactoferrin, a potent tryptase inhibitor, abolishes late-phase airway responses in allergic sheep. American Journal of Respiratory and Critical Care Medicine, 156(2 I), 375–381. https://doi.org/10.1164/ajrccm.156.2.9607012

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free