Effect of Albuterol Isomers on TNF‐alpha; Induced ICAM‐1 and Eotaxin Expression in Human Parasympathetic Neurons

Abstract

Airway parasympathetic neurons express ICAM‐1 and eotaxin which are required for eosinophil recruitment to the nerves. Major basic protein released by eosinophils blocks inhibitory neuronal M2 muscarinic receptors, increasing acetylcholine release and potentiating reflex bronchoconstriction. TNF‐α induces eotaxin and ICAM‐1 in parasympathetic neurons. Here we test whether albuterol, which is used to treat asthma, changes TNF‐α induced eotaxin and ICAM‐1 expression. Airway parasympathetic neurons were isolated from human trachea and grown in serum‐free medium for 1 week. Cells were incubated with 1uM of either R‐albuterol (the active isomer), S‐albuterol (the inactive isomer) or RS‐albuterol for 90 minutes before addition of 2ng/ml TNF‐α for another 4 hours. In the absence of TNF‐α baseline eotaxin and ICAM‐1 expression was not changed by any isomer of albuterol as measured by real time RT‐PCR. TNF‐α induced ICAM‐1 expression was inhibited by R‐albuterol but not by S or R,S‐albuterol. TNF‐α induced eotaxin expression was not inhibited by any isomer of albuterol. The suppressive effect of R‐albuterol on neural ICAM‐1 expression may decrease eosinophil recruitment to the airway nerves, thereby decreasing reflex bronchoconstriction.Funded by a grant from Sepracor Inc. and grants from NIH: HL55543, HL54659, HL071795, ES014601