Source: International Congress 2014 – COPD: points to ponder
Disease area: Airway diseases

Abstract

Introduction During asthma exacerbation, plasma circulating coagulant factor X (FX) enters the inflamed airways and is activated (FXa). Like thrombin, FXa activates the protease activated receptor-1 (PAR-1), and may have an important role in asthma. Extracellular annexin A2 is also implicated in PAR-1 signalling.Aim To investigate the PAR-1-mediated effects of FXa on airway smooth muscle (ASM) cell function.Methods Human ASM cells were incubated with FX, FXa (0.5-50 nM) and thrombin (300 mU/mL). PAR-1 and annexin A2 were targeted by siRNA or functional blocking antibodies. Thrombin and PAR-1 were inhibited using hirudin and SCH79797, respectively. Levels of interleukin-6 (IL-6) and cell proliferation were assessed by ELISA (24 h) and cell enumeration (48 h) respectively. Immunohistochemistry was used to evaluate the distribution and levels of annexin A2 and S100A10 in airway biopsies of asthmatics and controls. S100A10 is a binding partner of annexin A2 required for its extracellular trafficking.Results FXa, but not FX, stimulated SCH79797-sensitive ASM IL-6 production and cell proliferation. FXa effects were partially attenuated by hirudin, suggesting FXa converts ASM pro-thrombin to thrombin. Targeting annexin A2 attenuated FXa-, but not thrombin-stimulated ASM function. In airway biopsies, annexin A2 was detected in the periphery of the ASM bundle. Although annexin A2 levels appeared to be similar in the airways of asthmatics and controls, S100A10 levels were increased in severe asthma.Conclusion These findings establish FXa as a potentially important asthma mediator, stimulating ASM function, through actions requiring PAR-1 and annexin A2.

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Citations should be made in the following way:
M. Schuliga, T. Harris, S. Royce, A. Stewart (Parkville, Clayton, Australia). LATE-BREAKING ABSTRACT: The coagulant factor Xa induces PAR-1 and annexin A2-dependent airway smooth muscle cytokine production and cell proliferation.. Eur Respir J 2014; 44: Suppl. 58, 3624

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