OpenSSL SSL_connect: Connection reset by peer in connection to v2.sherpa.ac.uk:443 PuSH - Publication Server of Helmholtz Zentrum München: Neutrophil and monocyte kinetics play critical roles in mouse peritoneal adhesion formation.

PuSH - Publication Server of Helmholtz Zentrum München

Tsai, J.M.* ; Shoham, M.* ; Fernhoff, N.B.* ; George, B.M.* ; Marjon, K.D.* ; McCracken, M.N.* ; Kao, K.S.* ; Sinha, R.* ; Volkmer, A.K.* ; Miyanishi, M.* ; Seita, J.* ; Rinkevich, Y. ; Weissman, I.L.*

Neutrophil and monocyte kinetics play critical roles in mouse peritoneal adhesion formation.

Blood Adv. 3, 2713-2721 (2019)
Publ. Version/Full Text DOI PMC
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Peritoneal adhesions are pathological fibroses that ensnare organs after abdominal surgery. This dense connective tissue can cause small bowel obstruction, female infertility, and chronic abdominal pain. The pathogenesis of adhesions is a fibrotic response to tissue damage coordinated between mesothelial cells, fibroblasts, and immune cells. We have previously demonstrated that peritoneal adhesions are a consequence of mechanical injury to the mesothelial layer sustained during surgery. Neutrophils are among the first leukocytes involved in the early response to tissue damage. Here, we show that when subjected to mechanical stress, activated mesothelial cells directly recruit neutrophils and monocytes through upregulation of chemokines such as CXCL1 and monocyte chemoattractant protein 1 (MCP-1). We find that neutrophils within the adhesion sites undergo cell death and form neutrophil extracellular traps (NETosis) that contribute to pathogenesis. Conversely, tissue-resident macrophages were profoundly depleted throughout the disease time course. We show that this is distinct from traditional inflammatory kinetics such as after sham surgery or chemically induced peritonitis, and suggest that adhesions result from a primary difference in inflammatory kinetics. We find that transient depletion of circulating neutrophils significantly decreases adhesion burden, and further recruitment of monocytes with thioglycolate or MCP-1 also improves outcomes. Our findings suggest that the combination of neutrophil depletion and monocyte recruitment is sufficient to prevent adhesion formation, thus providing insight for potential clinical interventions.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 2473-9529
e-ISSN 2473-9537
Journal Blood advances
Quellenangaben Volume: 3, Issue: 18, Pages: 2713-2721 Article Number: , Supplement: ,
Publisher American Society of Hematology
Publishing Place Washington, DC
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)