Lactoferrin Inhibits Tryptase.


Tryptase has been in the news a bit here lately as being elevated in ME/CFS and other related illnesses.

Tryptase is the main diagnostic criteria for systemic mastocytosis but the level is not usually elevated in MCAS.

But it is interesting that lactoferrin strongly inhibits tryptase and thus might improve symptoms for at least a subset, especially those with asthma.

Lactoferrin is pretty cheap and readily available as a supplement so that is all positive for a trial too.

Am J Respir Crit Care Med. 1997 Aug;156(2 Pt 1):375-81.
Lactoferrin, a potent tryptase inhibitor, abolishes late-phase airway responses in allergic sheep.


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 (Ki' 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 phosphate-buffered 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.

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