Proliferation is not increased in airway myofibroblasts isolated from asthmatics

¹ Dept of Pharmacology, University of Melbourne, Victoria, Australia 3010
² Dept of Thoracic Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia, 3052
³ Dept of Respiratory Medicine, Royal Children's Hospital, Parkville, Victoria, Australia, 3052
⁴ Dept of Medicine, Monash University, Victoria, Australia, 3168.

	Abstract

Airway mesenchymal cells such as myofibroblasts and airway smooth muscle cells contribute to inflammation, airway remodelling and hyperresponsiveness in asthma by excessive proliferation and inflammatory mediator production.

Using endobronchial biopsies obtained from both non-asthmatic and asthmatic subjects, in situ proliferation was assessed by immunostaining for cyclin D1. The number of immunoreactive cells increased with asthma severity and was restricted to the epithelium and sub-epithelial connective tissue. Despite increases in smooth muscle area, cyclin D1 was not detected in cells in intact muscle bundles.

Biopsy-derived cell cultures were characterised as predominantly myofibroblasts, and assessed to determine if proliferation and cytokine production varied with asthma status. Cell enumeration showed that basal proliferation was similar in cells from non-asthmatics and asthmatics and mitogenic responses to FGF-2, thrombin or serum were either lesser or unchanged in cells from asthmatics. Interleukin (IL)-1-dependent GM-CSF and IL-8 release was increased in cell supernatants from asthmatics.

Thus, increased rates of cellular proliferation identified in situ in the asthmatic airway occurred outside the expanded smooth muscle compartment. Although reduced proliferative responses were observed in cultured myofibroblasts from asthmatics, the increased cytokine production by these cells suggests that this contributes to and may perpetuate ongoing inflammation in asthma.