Cross-talk between coagulation and inflammation in COPD. The role of Factor XIII

Abstract

Background: Components of the coagulation system, such as fibrin polymerization, may markedly modulate inflammatory processes. Factor XIII (FXIII), a protein responsible for fibrin polymerization, is modulated by CXCR3, an immune amplifier receptor that is upregulated in COPD, suggesting that FXIII might be a proinflammatory factor in COPD.

Aim: To investigate whether the FXIII-CXCR3 complex is involved in the inflammatory process of COPD.

Methods: In lung specimens from 22 smokers with COPD (COPD) [FEV₁:55±15(%)], 14 smokers without COPD (noCOPD) and 11 nonsmokers (NS), the expression of FXIII and CXCR3 and the number of CD8⁺Tcells were quantified by immunohistochemistry in alveolar macrophages (FXIII⁺AM%), in the alveolar walls (FXIII⁺cells/mm and CD8⁺Tcells/mm) and in lung tissue (CXCR3⁺cells/mm²).

Results: FXIII⁺AM were increased in COPD [75(25-98)%] compared to noCOPD [45(21-97) p=0.04)] and NS [20(0-5) p=0.0001]. In the alveolar walls, FXIII and CD8⁺Tcells were increased in COPD [4(1-8) FXIII⁺cell/mm, 7(1-13) CD8⁺Tcell/mm] compared to NS [1(0-4) FXIII⁺cell/mm, 3(1-3) CD8⁺Tcell/mm; p<0.05]. This pattern was paralleled by CXCR3 expression in lung tissue, that was increased in COPD [44(5-100) cell/mm²] and noCOPD [35(25-50)] compared to NS [9(8-32) p<0.05], and was related to FXIII expression (p=0.01). FXIII expression was inversely related to FEV₁/FVC(%) (r=-0.46 p=0.006).

Conclusion: FXIII, an important coagulation factor, is upregulated in COPD and related to CXCR3 expression and to severity of airflow obstruction, suggesting that it could be implicated in the mechanisms leading to lung inflammation in COPD.