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Cytokines induce airway smooth muscle cell hyperresponsiveness to contractile agonists
  1. Yassine Amrani,
  2. Reynold A Panettieri Jr
  1. Pulmonary and Critical Care Division, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104–4283, USA
  1. Dr Y Amrani.

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A variety of cell types that reside in or infiltrate the inflamed submucosa potentially interact with airway smooth muscle cells and alter myocyte function. Eosinophils, macrophages and, particularly, lymphocytes are postulated as being critical in the initiation and perpetuation of the asthmatic response. One mechanism by which immunocytes exert their effects is the production of proinflammatory mediators that may act directly or indirectly on ASM cells. Several cytokine mRNAs and proteins have been detected within the airways of asthmatic subjects. The precise role of these cytokines in altering myocyte function has recently been the focus of a new line of research. Although cytokines have been reported to inhibit β adrenergic receptor responsiveness in airway smooth muscle cells1 and alter mitogen induced myocyte growth,2 this article will review new evidence that suggests that cytokines also modulate contractile agonist induced calcium signalling in human airway smooth muscle cells.

Effect of cytokines on agonist induced calcium responses

Airway smooth muscle in vivo is either electrically quiescent or generates slow waves and some active tone, but does not generate action potentials under resting conditions or when stimulated by neurotransmitters or autocoids. Excitatory stimulation, whether neural, hormonal, or due to the release of autocoids, results in a graded depolarisation and increase in tone in the muscle. Since excitatory and inhibitory stimuli are imposed on a tissue with little intrinsic contractile tone, the degree of muscle stimulation (and bronchodilation) will be the summated effect of bronchoconstrictor and bronchodilator stimuli.

Activation of an airway smooth muscle cell by a bronchoconstrictor induces a rapid rise in the intracellular concentration of calcium, associated with the release of intracellular calcium stores, to a peak level roughly 10 times higher than the resting level (from 100 nM to more than 1 μM at maximum agonist concentration) as shown in fig 1. Following this peak the calcium …

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