Proliferative response of airway smooth muscle cells to macrophage-derived products

Brown Norway rats show increased airway smooth muscle content following repeated allergen challenges. Macrophages synthesize many growth factors in vitro which potentially stimulate proliferation of airway smooth muscle cells. Leukotriene C$sb4$, an important mediator of allergic airway responses, can stimulate macrophages to release platelet-derived growth factor (PDGF) which is a potent stimulator of proliferation. The purpose of this study was to investigate the role of the macrophage in the proliferative response of airway smooth muscle cells leading to airway remodelling. Macrophages were harvested from 7- to 9-week-old male Brown Norway rats, allowed to adhere to plastic 25cm$sp2$ culture flasks for 25 minutes, rinsed with sterile PBS at 37$sp circ$C to wash off cells other than macrophages and maintained in short-term culture in serum-free medium. Airway smooth muscle cells were also harvested and cultured. Supernatant from macrophages significantly stimulated airway smooth muscle cell proliferation 5-fold as compared to controls (p $<$ 0.05). This stimulation was affected neither by the addition of the cyclooxygenase inhibitor ASA, nor by the addition of the LTD$sb4$ inhibitor MK-571. However, stimulation was decreased by the addition of the PDGF inhibitor suramin, as well as by an anti-PDGF polyclonal antibody. Maximal inhibition observed with antibody was 34% (p $<$ 0.01). We conclude that macrophages have the ability to stimulate airway smooth muscle cell proliferation by releasing growth factors, that one of these growth factors is PDGF, and that PDGF contributes 34% of the total airway smooth muscle cell proliferation. Therefore, it is likely that macrophages play an important role in airway remodelling and that this airway remodelling may be an important component in the pathology of asthma. (Abstract shortened by UMI.