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Identifier |
000401037 |
Title |
Βλάβη ισχαιμίας-επαναιμάτωσης στο γαστρεντερικό σύστημα και ο ρόλος του συμπληρώματος |
Alternative Title |
Complement depletion protects lupus -prone mice from ischemia-reperfusion -initiated organ injury |
Author
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Ιωάννου, Αντώνης
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Thesis advisor
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Παπαδάκης, Κωνσταντίνος
Τσώκος, Γεώργιος
Καρδάσης, Δημήτριος
Σιδηρόπουλοε, Πρόδρομος
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Reviewer
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Γουλιέλμος, Γιώργος
Μπερτσιάς, Γεώργιος
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Abstract |
1st MODULE: COMPLEMENT DEPLETION PROTECTS LUPUS-PRONE MICE
FROM ISCHEMIA-REPERFUSION-INITIATED ORGAN INJURY.
Ischemia-reperfusion (IR) injury causes a vigorous immune response that is
amplified by complement activation, leading to local and remote tissue damage.
Using MRL/lpr mice, which are known to experience accelerated tissue damage
after mesenteric IR injury, we sought to evaluate whether complement inhibition
mitigates organ damage.
We found that complement depletion with cobra venom factor protected mice
from local and remote lung tissue damage. Protection from injury was associated
with less complement (C3) and membrane attack complex deposition, less
neutrophil infiltration, and lower levels of local proinflammatory cytokine production.
In addition, complement depletion was able to decrease the level of oxidative stress
as measured by glutathione peroxidase 1 mRNA levels and superoxide dismutase
activity. Furthermore, blockage of C5a receptor protected MRL/lpr mice from local
tissue damage, but not from remote lung tissue damage.
In conclusion, although treatments with cobra venom factor and C5a receptor
antagonist were able to protect mice from local tissue damage, treatment with C5a
receptor antagonist was not able to protect mice from remote lung tissue damage,
implying that more factors contribute to the development of remote tissue damage
after IR injury. These data also suggest that complement inhibition at earlier, rather
than late, stages can have clinical benefit in conditions that are complicated with IR
injury.
2nd MODULE: THE ROLE OF PLATELET FACTOR 4 IN LOCAL AND REMOTE
TISSUE DAMAGE IN A MOUSE MODEL OF MESENTERIC ISCHEMIAREPERFUSION
INJURY.
The robust inflammatory response that occurs during ischemia reperfusion
(IR) injury recruits factors from both the innate and adaptive immune systems.
However the contribution of platelets and their products such as Platelet Factor 4
(PF4; CXCL4), during the pathogenesis of IR injury has not been thoroughly
investigated.
We show that a deficiency in PF4 protects mice from local and remote tissue
damage after 30 minutes of mesenteric ischemia and 3 hours of reperfusion in PF4-
/- mice compared to control B6 mice. This protection was independent from Ig or
complement deposition in the tissues. However, neutrophil and monocyte infiltration
were decreased in the lungs of PF4-/- mice compared with B6 control mice. Plateletdepleted
B6 mice transfused with platelets from PF4-/- mice displayed reduced
tissue damage compared with controls. In contrast, transfusion of B6 platelets into
platelet depleted PF4-/- mice reconstituted damage in both intestine and lung
tissues. We also show that PF4 may modulate the release of IgA. Interestingly, we
show that PF4 expression on intestinal epithelial cells is increased after IR at both
the mRNA and protein levels.
In conclusion, these findings demonstrate that may PF4 represent an
important mediator of local and remote tissue damage.
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Language |
Greek |
Subject |
Autoimmunity |
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Αιμοπετάλια |
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Αυτοάνοσα νοσήματα |
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Λεπτό έντερο |
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Συστηματικός ερυθηματώδης λύκος |
Issue date |
2015-03-27 |
Collection
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School/Department--School of Medicine--Department of Medicine--Doctoral theses
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Type of Work--Doctoral theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/e/4/a/metadata-dlib-1463736914-109257-18333.tkl
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Views |
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