title: Mechanism of cooperative effects of rhinovirus and atopic sensitization on airway responsiveness.
abstract: 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-1beta. 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 FcepsilonRII (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 FcepsilonRII 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.
authors.affiliation: 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, PA 19104, USA. grunstein@email.chop.edu
authors.forename: M M
authors.initials: MM
authors.lastname: Grunstein
authors.forename: H
authors.initials: H
authors.lastname: Hakonarson
authors.forename: R L
authors.initials: RL
authors.lastname: Hodinka
authors.forename: N
authors.initials: N
authors.lastname: Maskeri
authors.forename: C
authors.initials: C
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Chuang
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D019264:Adoptive Transfer / Q000379:methods; D000403:Airway Resistance / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects / Q000276:immunology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007106:Immune Sera / Q000276:immunology / Q000494:pharmacology; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000096:biosynthesis; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects / Q000276:immunology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D010850:Picornaviridae Infections / Q000276:immunology; D011817:Rabbits; D017455:Receptors, IgE / Q000096:biosynthesis; D012229:Rhinovirus / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D007106:Immune Sera; D007375:Interleukin-1; D016169:Lymphocyte Function-Associated Antigen-1; D017455:Receptors, IgE; D018799:Intercellular Adhesion Molecule-1; D000109:Acetylcholine