• R A Panettieri.
• Pulmonary and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. rap@mail.med.upenn.edu
• Am. J. Respir. Crit. Care Med. 1998 Nov 1; 158 (5 Pt 3): S133-40.

AbstractAsthma as well as bronchiolitis obliterans and chronic bronchitis are chronic lung diseases characterized by airflow obstruction and airway inflammation. Although asthma typically induces reversible airflow obstruction, in some patients airflow obstruction becomes irreversible. The irreversible airway remodeling that occurs in asthma has been attributed in part to increased smooth muscle mass. However, the precise mechanisms regulating increases in myocyte number in vivo remain unknown. Frequent stimulation of airway smooth muscle by contractile agonists, inflammatory mediators, and growth factors may contribute to stimulation of myocyte proliferation. The recognition of phosphatidylinositol 4,5-bisphosphate hydrolysis as a ubiquitous receptor-activated signaling mechanism has led to the discovery that phospholipids, in particular 3-PI, may play a critical role in signaling cell growth. Infiltrating inflammatory cells may indirectly stimulate myocyte growth and activate PI 3-kinase through secretion of agonists and growth factors. In addition, new evidence reveals that direct cell- cell interaction between immunocytes and airway smooth muscle may also modulate airway smooth muscle cell function. Studies have shown that activated T lymphocytes can adhere to cultured airway smooth muscle, and the functional consequence of this adherence is the upregulation of cell adhesion molecules and the stimulation of DNA synthesis in human airway smooth muscle cells. The identification of the critical regulatory sites that mediate airway smooth muscle cell proliferation or modulate cell adhesion molecule expression in these cells may improve our understanding of the mechanisms that regulate airway inflammation and possibly provide new therapeutic approaches to alter airway remodeling seen in patients with chronic airflow obstruction.

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