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P186 Mast cell mediators stimulate human airway smooth muscle growth, a feature of airway remodelling in asthma via matrix metalloproteinase (MMP-1) activity
  1. S Naveed,
  2. D Shaw,
  3. SR Johnson
  1. University of Nottingham, Nottingham, UK


Introduction and Objective : Increased airway smooth muscle (ASM) mass and infiltration by mast cells are key features of airway remodelling in asthma. We tested a hypothesis to investigate the relationship between ASM growth, mast cell mediators and the matrix metalloproteinase MMP-1 activity.

Methods : Primary ASM cultures were derived from a healthy subject. ASM cells were cultured for up to 2 days firstly in the presence and then in absence of serum and treated with conditioned media either collected from activated mast cells cultures or inactive/ unstimulated mast cells cultures. Mast cells were grown in suspension and activated using phorbol 12-myristate 13-acetate (PMA) and calcium ionophore (A23187) to release serine proteases such as histamine, beta-tryptase and chymase etc. We also performed western blots to determine MMP-1 activity in the supernatants of ASM cultures.

Results ASM cells treated with stimulated mast cells conditioned media showed increased cell proliferation by almost 2 folds after 48 hours of incubation under serum free conditions confirmed by cell counting and MTT assay in comparison with untreated airway smooth muscle cells or ASM cells treated with inactive/ unstimulated mast cells culture media.

Furthermore our experiments showed that matrix metalloproteinase (MMP -1) levels and activity was significantly increased in ASM cultures treated with activated mast cells as compared to other two control conditions as mentioned earlier.

Conclusion These findings clearly indicate role of mast cell proteases in ASM proliferation and therefore airway remodeling in asthma, a mechanism that perhaps is modulated by MMP-1 activity. We further suggest that the pathway will prove susceptible to pharmacological intervention for treatment of chronic asthma.

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