The role of tryptase in immediate cutaneous responses in allergic sheep. Molinari, J. F., W. R. Moore, J. Clark, R. Tanaka, J. H. Butterfield, and W. M. Abraham. Pulmonary Division, University of Miami at Mount Sinai Medical Center, Miami Beach, Florida USA; Arris Pharmaceutical Corp., South San Francisco, California USA; Mayo Clinic, Rochester, Minnesota, U.S.A.
APStracts 2:0347A, 1995.
In this study, we used a specific tryptase inhibitor, APC 366 [N-(1 -hydroxy-2-napthoyl)-L-arginyl-L-prolinamide hydrochloride] to investigate the effect of intradermally administered tryptase and tryptase released by antigen challenge on the immediate cutaneous reaction (ICR) in allergic sheep. The surface area of cutaneous wheals produced by intradermal injections (0.05 ml) of 1 and 10 ng tryptase alone, tryptase combined with 3U heparin (tryptase:heparin) or Ascaris suum antigen (10-5 dilution) with or without pretreatment with APC 366 (1 mg/ml) were measured at 20 and 60 min after challenge. Intradermal injections of 1 and 10 ng tryptase alone (n=7) produced an ICR of /=70% at all times (n=8), but had no effect on the histamine-induced ICR (n=3). A combination of the histamine H1 antagonist, chlorpheniramine (2 mg/kg, iv) and the H2 antagonist metiamide (3 mg/kg, iv) given 40 min before challenge (n=8) inhibited the response to 1 and 10 ng tryptase:heparin by 42% and 62% at 20 min and 96% and 86% at 60 min, respectively (all, P&LT0.05). APC 366 also blocked the ICR to Ascaris suum antigen by 68% (p&LT0.05) in 9 sheep. These results indicate that intradermal injection of tryptase:heparin can induce an ICR. This ICR can be inhibited by APC 366 or a combination of the histamine H1 and H2 antagonists suggesting that the tryptase response is mediated by histamine. APC 366 also blocks the mast cell mediated ICR to intradermally injected Ascaris suum antigen. Collectively, these results suggest that tryptase may modulate mast cell histamine release. 

Received 27 March 1995; accepted in final form 17 July 1995.
APS Manuscript Number A331-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.