RT Journal Article
SR Electronic
T1 Bleomycin-induced remodeling – Inflammation and fibrosis are developing in parallel during initiation
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP p674
VO 38
IS Suppl 55
A1 Kristina Rydell-Törmänen
A1 Gunilla Westergren-Thorsson
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/p674.abstract
AB Background: Pulmonary fibrosis is a facet of Diffuse Parenchymal Lung Disease and has been considered a sequel to chronic inflammation. Yet the relation between connective tissue and immune system during the initiation phase has not been thoroughly investigated. Our aim was to investigate the initiation phase and the interplay between immune system and connective tissue.Methods: C57/Bl6 mice were given subcutaneous bleomycin injections (controls received saline) 3 times/week for 1, 2, 3 and 4 weeks. Following sacrifice, lungs were embedded in paraffin and 4 μm thick sections were used for analysis of lung parenchyma; Masson Trichrome (total collagen) and immunohistochemistry to detect neutrophils, macrophages and B-cells.Results: Total collagen was significantly increased at 1, 2 and 4 weeks. A transient neutrophilia was found at 1w (2779±820 cells/mm2), but no difference compared to controls was found at 2, 3 and 4w. Macrophages were significantly increased at 2w (135±29 cells/mm2), whereas B-cells were significantly decreased at 3 and 4w, compared to controls.Conclusions: Subcutaneous administration of bleomycin induced rapid pulmonary remodeling, exemplified by increased total collagen. The immune response was markedly different from the one following intratracheal administration, illustrated by the moderate and transient neutrophilia. Increase of macrophages at 2w in combination with decreased neutrophils suggests ongoing clearance. Decrease of B-cells may suggest migration to lymphoid organs, thus initiation of an adaptive immune response. In summary, we found fibrosis and inflammation occurring in parallel, both present early in the development of pulmonary fibrosis.