Acute pancreatitis, from local defense to remote organ injury
Författare
Summary, in English
Heparan sulfate (HS) is a common component of extracellular matrix which lines the ductal cells in the pancreas. During the process of the disease, active enzymes in the pancreas will cause shedding of HS.
We have shown that HS is able to start an inflammatory response in the pancreas. This response was mediated via Toll like receptor-4 and involved both MyD88-dependent and –independent pathways. We propose that HS has a role in the monitoring of pancreatic tissue well-being.
Acute lung injury is the most common extra-pancreatic complication in the acute pancreatitis. Macrophages are a heterogeneous population based on their anatomical location and their micro-environment. Our data showed an enriched population of CD68+F4/80- macrophages in the lungs of animals with AP. This population had an increased expression of CD206 (a cell marker of alternatively activated macrophages) and CCR2 (the receptor for CCL2, an important chemoattractant for macrophages). Studying lung macrophages for different phenotypic markers, their polarization, activation and recruitment, in the context of acute lung injury, is a novel area to potentially identify interventions which may improve the outcome of acute lung injury.
Macrophages are a source of various remodeling cytokines including TGF-β.
TGF-β not only participates in the late phase of acute lung injury, but also might be active early in acute lung injury and potentially could contribute to the development of pulmonary edema.
Our data showed an increase in the level of TGF-β1 in the lungs of the acute pancreatitis group early on but this was in parallel with an increase in the level of inhibitory Smad7. The level of Smad7 was back to the control level after 24 h when there was an increase in the nuclear translocation of phosphorylated Smad2. Our findings suggest that TGF-β signaling pathway can be activated in the early phase of ALI due to AP and may have a contributing role in the pathogenesis of lung injury. Therefore, TGF-β signaling pathway can represent a potential strategy to be used in the future treatment of ALI.
Avdelning/ar
Publiceringsår
2013
Språk
Engelska
Publikation/Tidskrift/Serie
Lund University Faculty of Medicine Doctoral Dissertation Series
Volym
2013:23
Fulltext
Dokumenttyp
Doktorsavhandling
Förlag
Surgery (Lund)
Ämne
- Surgery
Nyckelord
- Acute pancreatitis
- heparan sulfate
- damage associated molecular patterns
- toll-like receptor4
- MyD88
- IRF-3
- acute lung injury
- macrophages
- transforming growth factor-beta
- Smad
Status
Published
Handledare
- Roland Andersson
- Jakob B Axelsson
- Ann Rosendahl
ISBN/ISSN/Övrigt
- ISSN: 1652-8220
- ISBN: 978-91-87189-92-0
Försvarsdatum
8 mars 2013
Försvarstid
13:00
Försvarsplats
Belfrage lecture hall, BMC D15, Lund
Opponent
- Rachel Chambers