Tissue repair in lung disorders

Annika Andersson Sjöland

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

228 Nedladdningar (Pure)

Sammanfattning

The remodeling phase of tissue repair in lung disorders such as idiopathic pulmonary disease, asthma, obliterative bronchiolitis, and after lung transplantation is not well understood. One of the key players in fibrosis is the fibroblast and its progenitor, the fibrocyte. The fibroblast is the main producer of extracellular matrix molecules such as collagen, versican, perlecan, biglycan, and decorin. Fibrocytes are recruited from the bone marrow to the site of injury. It is possible that the stromal cell-derived factor-1/CXCL12 builds up in a gradient to recruit CXCR4 expressing fibrocytes, at least in the case of idiopathic pulmonary fibrosis. Patients with obliterative bronchilitis have an enlarged vessel lumen and a larger endothelial layer area, which has been shown to be correlated to more fibrocytes in the tissue. A correlation was found between the numbers of fibrocytes identified in tissue and structural changes in the lung. In idiopathic pulmonary fibrosis, a correlation was found between numbers of fibrocytes and numbers of fibroblastic foci, and in patients with obliterative bronchiolitis there was a correlation between fibrocyte numbers and thickening of the alveolar parenchyma. Eventually the fibrocyte enters the tissue and can differentiate into a fibroblast.

Matrix production by fibroblasts in patients who have undergone lung transplantation and in asthmatic subjects involves both the central and the distal parts of the lung. In lung-transplanted patients, the production of proteoglycans in the distal part was found to be double that in the central part. Versican production was particularly elevated compared to controls. The production of proteoglycans was further correlated with proliferation rate. A common feature of fibroblasts in patients after lung transplantation and asthmatic subjects was that these cells proliferated more slowly than in control subjects. Distally-derived fibroblasts from asthmatic subjects produced more veriscan, were immobile, and had many protrusions. The distal parts of the lungs were also rich in collagen.

A better understanding of fibrocyte and fibroblast function will help us to characterise the mechanisms behind idiopathic pulmonary disease, asthma, obliterative bronchiolitis. This knowledge can then be applied to other types of fibrotic disorders.
Originalspråkengelska
KvalifikationDoktor
Tilldelande institution
  • Lungmedicin, allergologi och palliativ medicin
Handledare
  • Bjermer, Leif, handledare
  • Westergren-Thorsson, Gunilla, handledare
  • Eriksson, Leif, handledare
Tilldelningsdatum2009 dec. 11
Förlag
ISBN (tryckt)978-91-86443-11-5
StatusPublished - 2009

Bibliografisk information

Defence details

Date: 2009-12-11
Time: 09:00
Place: Belfragesalen, D15, BMC, Lund

External reviewer(s)

Name: Pejler, Gunnar
Title: [unknown]
Affiliation: Uppsala Universitet

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Ämnesklassifikation (UKÄ)

  • Lungmedicin och allergi
  • Cell- och molekylärbiologi

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