Heparin effect in alveolar cells and macrophages in an acute lung injury model

Abstract

Introduction: Acute Lung Injury (ALI) is characterized by a promptly release of proinflammatory mediators started by macrophages that propagate the coagulant response. Anticoagulants could be effective for their anti-inflammatory effect additionally their anticoagulant activity. Objective: To evaluate the effect of heparin in human alveolar cells and macrophages after induce an ALI. Methods: Human alveolar primary cells and alveolar macrophages from pulmonary biopsies were seeded. Heparin (100 UI/ml) was administered to the cells after the induction of an ALI with a pro-inflammatory stimulus (Cytomix: mix of TNFα, IL1β and IFNγ; 50 ng/ml). The effect of heparin was assessed by the analysis of proinflammatory markers (IL12p40 and iNOS), cell proliferation and permeability (measuring transmembrane resistance). Data are expressed as mean±SEM (units are relative to the expression of control group). Statistical analysis was performed using One-Way-ANOVA and post-hoc (Newman Keuls) test. Statistical significance p≤0.05 is considered. Results: Heparin was able to modify the inflammatory response of both cell populations, decreasing it significantly in the case of macrophages ( iNOS: Control:1±0.09, Injured group:41.68±4.86, Heparin group:0.54±0.06. IL12p40: Control:1±0.11, Injured group:46.74±4.32, Heparin group:0.15±0.009). The permeability of the monolayer and cell proliferation of alveolar cells did not show changes. Conclusions: Heparin has an immunomodulatory effect in alveolar cells and reduces inflammation in macrophages. This mechanism produced by heparin could have a beneficial effect in ALI.