Cooperative effects of rhinovirus and atopic sensitization on airway responsiveness.
Grunstein, Michael M., Hakon Hakonarson, Richard L. Hodinka, Neil Maskeri, Cecilia
Kim, and Sing Chuang.
Divisions of Pulmonary Medicine and Allergy, Immunology, and Infectious Diseases,
Joseph Stokes, Jr. Research Institute, Children's Hospital of Philadelphia, University of
Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
APStracts 7:0249L, 2000.
To elucidate the mechanistic interplay between rhinovirus (RV) exposure and atopic
sensitization in regulating airway smooth muscle (ASM) responsiveness, isolated rabbit
ASM tissue and cultured human ASM cells were passively sensitized with sera from
atopic asthmatic or nonatopic nonasthmatic (control) subjects in the absence and presence
of inoculation with RV serotype 16. Relative to control subjects, atopic asthmatic serum-
sensitized and RV-inoculated ASM exhibited significantly increased contractility to
acetylcholine, impaired relaxation to isoproterenol, and enhanced release of the
proinflammatory cytokine interleukin-1ß. These effects were potentiated in atopic
asthmatic serum-sensitized ASM concomitantly inoculated with RV and inhibited by
pretreating the tissues with monoclonal blocking antibodies against intercellular adhesion
molecule (ICAM)-1 (CD54), the host receptor for RV serotype 16, or lymphocyte
function-associated antigen (LFA)-1 (CD11a/CD18), the endogenous counterreceptor for
ICAM-1. Moreover, RV inoculation was found to potentiate the induction of mRNA and
surface protein expression of FceRII (CD23), the low-affinity receptor for IgE, in atopic
asthmatic serum-sensitized ASM. Collectively, these observations provide new evidence
demonstrating that 1) RV exposure and atopic sensitization act cooperatively to
potentiate induction of proasthmatic changes in ASM responsiveness in association with
upregulated proinflammatory cytokine release and FceRII expression and 2) the effects of
RV exposure and atopic sensitization are mediated by cooperative ICAM-1-coupled
LFA-1 signaling in the ASM itself.
Received 24 June 2000; accepted in final form 1 August 2000
APS Manuscript Number L210-0.
Article publication pending Am J Physiol Lung Cell Mol Physiol
ISSN 1080-4757 Copyright 2000 The American Physiological Society.
Published in APStracts on 7 November 2000