TY - JOUR
T1 - Cationic proteins alter smooth muscle function by an epithelium-dependent mechanism
AU - Coyle, A. J.
AU - Mitzner, W.
AU - Irvin, C. G.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1993
Y1 - 1993
N2 - Using a perfused guinea pig tracheal tube preparation, which allows the selective application of agonists to either the serosal or luminal surface, we have investigated whether two synthetic cationic proteins, poly-L-arginine and poly-L-lysine, can modify epithelium-dependent responses. With an intact epithelium, methacholine was ~150 times less potent when applied intraluminally than when applied extraluminally. This difference was abolished by chemically removing the epithelium with the detergent CHAPS. Intraluminal application of KCl induced a dose-related relaxation of a precontracted trachea, which was also abolished by epithelium removal. Perfusion of the luminal surface with cationic proteins for 1 h (10 μg/ml) increased the potency of intraluminally applied methacholine without modifying the responses to extraluminally applied methacholine. Cationic proteins also attenuated the relaxant effects of intraluminally applied KCl. These effects occurred in the absence of any overt epithelial cell damage. In contrast, when the serosal surface of the trachea was treated with poly-L- arginine, there was no modification of either methacholine-induced contraction or KCl-induced relaxation. The effects of poly-L-arginine were inhibited by coperfusion with the polyanions albumin (10 μg/ml) or heparin (100 μg/ml). In contrast to cationic proteins, intraluminal perfusion with a polyanion, poly-L-aspartate (10 μg/ml), failed to modify either methacholine-induced contraction or KCl-induced relaxation. Our data demonstrate that cationic proteins can modify epithelium-dependent responses in the airways. Although the precise mechanisms are unclear, a role is suggested for a charge-mediated interaction with the respiratory epithelium, resulting in airway smooth muscle dysfunction.
AB - Using a perfused guinea pig tracheal tube preparation, which allows the selective application of agonists to either the serosal or luminal surface, we have investigated whether two synthetic cationic proteins, poly-L-arginine and poly-L-lysine, can modify epithelium-dependent responses. With an intact epithelium, methacholine was ~150 times less potent when applied intraluminally than when applied extraluminally. This difference was abolished by chemically removing the epithelium with the detergent CHAPS. Intraluminal application of KCl induced a dose-related relaxation of a precontracted trachea, which was also abolished by epithelium removal. Perfusion of the luminal surface with cationic proteins for 1 h (10 μg/ml) increased the potency of intraluminally applied methacholine without modifying the responses to extraluminally applied methacholine. Cationic proteins also attenuated the relaxant effects of intraluminally applied KCl. These effects occurred in the absence of any overt epithelial cell damage. In contrast, when the serosal surface of the trachea was treated with poly-L- arginine, there was no modification of either methacholine-induced contraction or KCl-induced relaxation. The effects of poly-L-arginine were inhibited by coperfusion with the polyanions albumin (10 μg/ml) or heparin (100 μg/ml). In contrast to cationic proteins, intraluminal perfusion with a polyanion, poly-L-aspartate (10 μg/ml), failed to modify either methacholine-induced contraction or KCl-induced relaxation. Our data demonstrate that cationic proteins can modify epithelium-dependent responses in the airways. Although the precise mechanisms are unclear, a role is suggested for a charge-mediated interaction with the respiratory epithelium, resulting in airway smooth muscle dysfunction.
KW - airway hyperresponsiveness
KW - epithelium
KW - epithelium-dependent relaxing factor
KW - trachea
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U2 - 10.1152/jappl.1993.74.4.1761
DO - 10.1152/jappl.1993.74.4.1761
M3 - Article
C2 - 8514694
AN - SCOPUS:0027294623
SN - 8750-7587
VL - 74
SP - 1761
EP - 1768
JO - Journal of applied physiology
JF - Journal of applied physiology
IS - 4
ER -