Lipopolysaccharide-induced goblet cell hypersecretion in the guinea
pig trachea: inhibition by macrolides.
Tamaoki, Jun, Kiyoshi Takeyama, Isao Yamawaki, Mitsuko Kondo, and
Kimio Konno.
First Department of Medicine, Tokyo Women's Medical College, Tokyo
162, Japan
APStracts 3:0167L, 1996.
We studied the effects of macrolides on lipopolysaccharide (LPS)
-induced airway goblet cell secretion in the guinea pig trachea. The
goblet cell secretion was assessed in histological sections of the
tracheal mucosa stained with Alcian blue and PAS by arbitrarily
determining mucus score, which is inversely related to the magnitude
of mucus discharge. Inhalation of Escheritia coli LPS (5 mg/kg)
caused a time-dependent decrease in mucus score, with the maximal
response being from 542 +/- 49 to 92 +/- 20 AU (arbitrary units, P
< 0.001) after 3 h, which was accompanied by an increase in
the number of neutrophils in the tracheal mucosa. The LPS-induced
mucus discharge was inhibited by oral clarithromycin (CAM) and
erythromycin (EM) in a dose-dependent manner (5 mg/kg and 10 mg/kg),
whereas amoxicillin (AMPC) and cefaclor (CCL) had no effect. Each CAM
and EM, but not AMPC or CCL, likewise attenuated the LPS-induced
recruitment of neutrophils. These results suggest that LPS stimulates
goblet cell secretion and neutrophil accumulation in the airways, and
that macrolides may be of value in protecting against neutrophil
-associated airway hypersecretion.
Received 29 May 1996; accepted in final form 14 August 1996.
APS Manuscript Number L155-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996