Abstract
BackgroundMajor basic protein released from eosinophils to airway parasympathetic nerves blocks inhibitory M2 muscarinic receptors on the parasympathetic nerves, increasing acetylcholine release and potentiating reflex bronchoconstriction. Recruitment of eosinophils to airway parasympathetic neurons requires neural expression of both intercellular adhesion molecular-1 (ICAM-1) and eotaxin. We have shown that inflammatory cytokines induce eotaxin and ICAM-1 expression in parasympathetic neurons.ObjectiveTo test whether the β2 agonist albuterol, which is used to treat asthma, changes TNF-alpha-induced eotaxin and ICAM-1 expression in human parasympathetic neurons.MethodsParasympathetic neurons were isolated from human tracheas and grown in serum-free medium for one week. Cells were incubated with either (R)-albuterol (the active isomer), (S)-albuterol (the inactive isomer) or (R,S)-albuterol for 90 minutes before adding 2 ng/ml TNF-alpha for another 4 hours (for mRNA) or 24 hours (for protein).Results and ConclusionsBaseline expression of eotaxin and ICAM-1 were not changed by any isomer of albuterol as measured by real time RT-PCR. TNF-alpha induced ICAM-1 expression was significantly inhibited by (R)-albuterol in a dose dependent manner, but not by (S) or (R,S)-albuterol. Eotaxin expression was not changed by TNF-alpha or by any isomer of albuterol. The β-receptor antagonist propranolol blocked the inhibitory effect of (R)-albuterol on TNF-alpha-induced ICAM-1 expression.Clinical ImplicationThe suppressive effect of (R)-albuterol on neural ICAM-1 expression may be an additional mechanism for decreasing bronchoconstriction, since it would decrease eosinophil recruitment to the airway nerves.
Highlights
Eosinophils are in contact with airway nerves in patients with asthma and in antigen challenged animals [1,2]
Baseline expression of eotaxin and intercellular adhesion molecular-1 (ICAM-1) were not changed by any isomer of albuterol as measured by real time RT-PCR
Clinical Implication: The suppressive effect of (R)-albuterol on neural ICAM-1 expression may be an additional mechanism for decreasing bronchoconstriction, since it would decrease eosinophil recruitment to the airway nerves
Summary
Eosinophils are in contact with airway nerves in patients with asthma and in antigen challenged animals [1,2]. ICAM-1 is important for eosinophil adhesion via LFA-1, a receptor found on eosinophils Both eotaxin and ICAM-1 are present on airway nerves in antigen-challenged guinea pigs and on cultured airway parasympathetic neurons [5,7]. Both can be induced by inflammatory cytokines [5,7,10,11]. Reducing ICAM-1 or blocking eotaxin expression on parasympathetic nerves relates to reduced parasympathetic nerves associated eosinophils, and reduced airway hyperreactivity [5,7,8]. Recruitment of eosinophils to airway parasympathetic neurons requires neural expression of both intercellular adhesion molecular-1 (ICAM-1) and eotaxin. We have shown that inflammatory cytokines induce eotaxin and ICAM-1 expression in parasympathetic neurons
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