Platelets and eosinophils in lung tissue remodelling

University dissertation from Stockholm : Karolinska Institutet, Department of Medicine

Abstract: Tissue injury and inflammation followed by effective repair restores normal function, but defective repair with associated tissue remodelling and fibrosis can lead to loss of organ function. Thus, interactions between inflammatory and mesenchymal cells in connection with the remodelling processes are of considerable importance with regards to the development of pulmonary disorders, since this interplay determines the outcome of the disease. At present, no clinical treatment for fibrosis is available and it is of considerable importance to improve our knowledge concerning the mechanisms that lead to tissue remodelling and fibrosis in order to develop effective therapeutic strategies. The present thesis was designed to explore the impact of two important inflammatory cells, platelets and eosinophils, on remodelling of lung tissue employing systems. Data are based on experimental models such as fibroblast-mediated contraction of collagen gels, which reflects the contractile process typical of tissue remodelling. In this model human lung fibroblasts are cultured in an artificial lung tissue consisting of type I collagen. The advantages of vivo and, furthermore, demonstrate more in vivo-like functional properties. To monitor fibroblast recruitment, which is also an important step in the remodelling process, we employed Boyden chambers with type I collagen coated filters. Platelets and eosinophils were cultured together with fibroblasts in collagen gels to explore the influence of these cells on gel contraction. Both platelets and lysate thereof stimulated fibroblastmediated contraction of collagen gels and both PDGF and TGF-

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