Role of heparin in pulmonary cell populations in an in-vitro model of acute lung injury

Background: In the early stages of acute respiratory distress syndrome (ARDS), pro-inflammatory mediators inhibit natural anticoagulant factors and initiate an increase in procoagulant activity. Previous studies proved the beneficial effects of heparin in pulmonary coagulopathy, which derive from its anticoagulant and anti-inflammatory activities, although it is uncertain whether heparin works. Understanding the specific effect of unfractioned heparin on cell lung populations would be of interest to increase our knowledge about heparin pathways and to treat ARDS. Methods: In the current study, the effect of heparin was assessed in primary human alveolar macrophages ( hAM), alveolar type II cells (hATII), and fibroblasts (hF) that had been injured with LPS. Results: Heparin did not produce any changes in the Smad/TGF beta pathway, in any of the cell types evaluated. Heparin reduced the expression of pro-inflammatory markers (TNF-alpha and IL-6) in hAM and deactivated the NF-k beta pathway in hATII, diminishing the expression of IRAK1 and MyD88 and their effectors, IL-6, MCP-1 and IL-8. Conclusions: The current study demonstrated that heparin significantly ameliorated the cells lung injury induced by LPS through the inhibition of pro-inflammatory cytokine expression in macrophages and the NF-k beta pathway in alveolar cells. Our results suggested that a local pulmonary administration of heparin through nebulization may be able to reduce inflammation in the lung; however, further studies are needed to confirm this hypothesis.