Complement inhibition decreases early fibrogenic events in the lung of septic baboons

Journal of Cellular and Molecular Medicine
Robert Silasi-MansatFlorea Lupu

Abstract

Acute respiratory distress syndrome (ARDS) induced by severe sepsis can trigger persistent inflammation and fibrosis. We have shown that experimental sepsis in baboons recapitulates ARDS progression in humans, including chronic inflammation and long-lasting fibrosis in the lung. Complement activation products may contribute to the fibroproliferative response, suggesting that complement inhibitors are potential therapeutic agents. We have been suggested that treatment of septic baboons with compstatin, a C3 convertase inhibitor protects against ARDS-induced fibroproliferation. Baboons challenged with 10(9) cfu/kg (LD50) live E. coli by intravenous infusion were treated or not with compstatin at the time of challenge or 5 hrs thereafter. Changes in the fibroproliferative response at 24 hrs post-challenge were analysed at both transcript and protein levels. Gene expression analysis showed that sepsis induced fibrotic responses in the lung as early as 24 hrs post-bacterial challenge. Immunochemical and biochemical analysis revealed enhanced collagen synthesis, induction of profibrotic factors and increased cell recruitment and proliferation. Specific inhibition of complement with compstatin down-regulated sepsis-induced fibrosis ge...Continue Reading

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Citations

Aug 20, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ellyse CipollaRagini Vittal
Sep 21, 2020·Journal of Cellular and Molecular Medicine·Florea LupuKenneth Dormer
Oct 27, 2016·Immunological Reviews·Daniel RicklinJohn D Lambris
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Jul 20, 2017·Proceedings of the National Academy of Sciences of the United States of America·Ravi Shankar KeshariFlorea Lupu
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Feb 20, 2021·Journal of Biochemical and Molecular Toxicology·Mustafa CicekMehmet Demir
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May 4, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Devendra Kumar, Neerja Trivedi
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Aug 5, 2021·ImmunoTargets and Therapy·Sofiane Fodil, Djillali Annane

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Datasets Mentioned

BETA
GSE23590

Methods Mentioned

BETA
Electrophoresis
antibody array
antibody
ELISA
GTPases
electron microscopy

Software Mentioned

IPA
Primer Express
- C1
Prism
ImageJ
limma
R
Imagene
Bioconductor
EZ

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