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

Kyle C. Elrod, William R. Moore, William M. Abraham, Richard D. Tanaka

Research output: Contribution to journalArticle

85 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)375-381
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume156
Issue number2 I
StatePublished - Sep 2 1997
Externally publishedYes

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Tryptases
Lactoferrin
Sheep
Bronchoconstriction
Heparin
Neutrophils
Asthma
Ascaris suum
Carbachol
Serine Proteases
Mast Cells
Inhalation
Gel Chromatography
Antigens
Lung
Proteins

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Lactoferrin, a potent tryptase inhibitor, abolishes late-phase airway responses in allergic sheep. / Elrod, Kyle C.; Moore, William R.; Abraham, William M.; Tanaka, Richard D.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 156, No. 2 I, 02.09.1997, p. 375-381.

Research output: Contribution to journalArticle

Elrod, Kyle C. ; Moore, William R. ; Abraham, William M. ; Tanaka, Richard D. / Lactoferrin, a potent tryptase inhibitor, abolishes late-phase airway responses in allergic sheep. In: American Journal of Respiratory and Critical Care Medicine. 1997 ; Vol. 156, No. 2 I. pp. 375-381.
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