Journal of Applied Physiology, Vol 79, Issue 6 1966-1970, Copyright © 1995 by American Physiological Society

ARTICLES

Role of tryptase in immediate cutaneous responses in allergic sheep

J. F. Molinari, 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 33140, USA.

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 areas of cutaneous wheals produced by intradermal injections (0.05 ml) of 1 and 10 ng tryptase alone, tryptase combined with 3 U 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 < or = 20% of that obtained after injection of histamine (5% wt/vol). Intradermal injection of tryptase-heparin (n = 7), however, resulted in 50 (1 ng) and 82% (10 ng) of the ICR to histamine (both, P < 0.05 vs. tryptase alone). APC-366 inhibited (P < 0.05) the ICR to 1 and 10 ng tryptase-heparin by > or = 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 by 96 and 86% at 60 min, respectively (all, P < 0.05). APC-366 also blocked the ICR to A. suum antigen by 68% (P < 0.05) in nine 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 A. suum antigen. Collectively, these results suggest that tryptase may modulate mast cell histamine release.

This article has been cited by other articles:

				M. T. Kasaian, D. D. Donaldson, L. Tchistiakova, K. Marquette, X.-Y. Tan, A. Ahmed, B. A. Jacobson, A. Widom, T. A. Cook, X. Xu, et al. Efficacy of IL-13 Neutralization in a Sheep Model of Experimental Asthma Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 368 - 376. [Abstract] [Full Text] [PDF]

				W. M. Abraham Tryptase: potential role in airway inflammation and remodeling Am J Physiol Lung Cell Mol Physiol, February 1, 2002; 282(2): L193 - L196. [Full Text] [PDF]

				S. He, M. D. A. Gaça, A. R. McEuen, and A. F. Walls Inhibitors of Chymase as Mast Cell-Stabilizing Agents: Contribution of Chymase in the Activation of Human Mast Cells J. Pharmacol. Exp. Ther., November 1, 1999; 291(2): 517 - 523. [Abstract] [Full Text]

				S. He, M. D. A. Gaça, and A. F. Walls A Role for Tryptase in the Activation of Human Mast Cells: Modulation of Histamine Release by Tryptase and Inhibitors of Tryptase J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 289 - 297. [Abstract] [Full Text]

				K. C. ELROD, W. R. MOORE, W. M. ABRAHAM, and R. D. TANAKA Lactoferrin, a Potent Tryptase Inhibitor, Abolishes Late-Phase Airway Responses in Allergic Sheep Am. J. Respir. Crit. Care Med., July 1, 1997; 156(2): 375 - 381. [Abstract] [Full Text]

				E. Tchougounova, E. Forsberg, G. Angelborg, L. Kjellen, and G. Pejler Altered Processing of Fibronectin in Mice Lacking Heparin. A ROLE FOR HEPARIN-DEPENDENT MAST CELL CHYMASE IN FIBRONECTIN DEGRADATION J. Biol. Chem., February 2, 2001; 276(6): 3772 - 3777. [Abstract] [Full Text] [PDF]