title: CD4+ T cells enhance the unloaded shortening velocity of airway smooth muscle by altering the contractile protein expression.
abstract: Abundant data indicate that pathogenesis in allergic airways disease is orchestrated by an aberrant T-helper 2 (Th2) inflammatory response. CD4(+) T cells have been localized to airway smooth muscle (ASM) in both human asthmatics and in rodent models of allergic airways disease, where they have been implicated in proliferative responses of ASM. Whether CD4(+) T cells also alter ASM contractility has not been addressed. We established an in vitro system to assess the ability of antigen-stimulated CD4(+) T cells to modify contractile responses of the Brown Norway rat trachealis muscle. Our data demonstrated that the unloaded velocity of shortening (Vmax) of ASM was significantly increased upon 24 h co-incubation with antigen-stimulated CD4(+) T cells, while stress did not change. Enhanced Vmax was dependent upon contact between the CD4(+) T cells and the ASM and correlated with increased levels of the fast (+)insert smooth muscle myosin heavy chain isoform. The levels of myosin light chain kinase and myosin light chain phosphorylation were also increased within the muscle. The alterations in mechanics and in the levels of contractile proteins were transient, both declining to control levels after 48 h of co-incubation. More permanent alterations in muscle phenotype might be attainable when several inflammatory cells and mediators interact together or after repeated antigenic challenges. Further studies will await new tissue culture methodologies that preserve the muscle properties over longer periods of time. In conclusion, our data suggest that inflammatory cells promote ASM hypercontractility in airway hyper-responsiveness and asthma.
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montréal, Québec, Canada, H2X 2P2.
authors.forename: Oleg S
authors.initials: OS
authors.lastname: Matusovsky
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montréal, Québec, Canada, H2X 2P2.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Nakada
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montréal, Québec, Canada, H2X 2P2.
authors.forename: Linda
authors.initials: L
authors.lastname: Kachmar
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montréal, Québec, Canada, H2X 2P2.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Fixman
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montréal, Québec, Canada, H2X 2P2 anne-marie.lauzon@mcgill.ca.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lauzon
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018920:Coculture Techniques; D003285:Contractile Proteins / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D018994:Myosin Light Chains / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D010047:Ovalbumin / Q000494:pharmacology; D011914:Rats, Inbred BN; D013154:Spleen / Q000166:cytology; D014132:Trachea / Q000502:physiology*
chemical_list: D003285:Contractile Proteins; D018994:Myosin Light Chains; D010047:Ovalbumin; D009219:Myosin-Light-Chain Kinase