PMID- 31519647
OWN - NLM
STAT- MEDLINE
DCOM- 20200814
LR  - 20201224
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 3
IP  - 18
DP  - 2019 Sep 24
TI  - Neutrophil and monocyte kinetics play critical roles in mouse peritoneal adhesion 
      formation.
PG  - 2713-2721
LID - 10.1182/bloodadvances.2018024026 [doi]
AB  - 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.
CI  - (c) 2019 by The American Society of Hematology.
FAU - Tsai, Jonathan M
AU  - Tsai JM
AUID- ORCID: 0000-0001-5868-2305
AD  - Institute for Stem Cell Biology and Regenerative Medicine and.
AD  - Department of Developmental Biology, School of Medicine, Stanford University, 
      Stanford, CA.
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, MA.
FAU - Shoham, Maia
AU  - Shoham M
AUID- ORCID: 0000-0003-4599-1015
AD  - Institute for Stem Cell Biology and Regenerative Medicine and.
FAU - Fernhoff, Nathaniel B
AU  - Fernhoff NB
AD  - Institute for Stem Cell Biology and Regenerative Medicine and.
FAU - George, Benson M
AU  - George BM
AUID- ORCID: 0000-0003-4031-0954
AD  - Institute for Stem Cell Biology and Regenerative Medicine and.
FAU - Marjon, Kristopher D
AU  - Marjon KD
AD  - Institute for Stem Cell Biology and Regenerative Medicine and.
FAU - McCracken, Melissa N
AU  - McCracken MN
AD  - Institute for Stem Cell Biology and Regenerative Medicine and.
FAU - Kao, Kevin S
AU  - Kao KS
AD  - Institute for Stem Cell Biology and Regenerative Medicine and.
FAU - Sinha, Rahul
AU  - Sinha R
AUID- ORCID: 0000-0001-7511-0798
AD  - Institute for Stem Cell Biology and Regenerative Medicine and.
FAU - Volkmer, Anne Kathrin
AU  - Volkmer AK
AD  - Department of Gynecology and Obstetrics, University Hospital Dusseldorf, 
      Dusseldorf, Germany.
FAU - Miyanishi, Masanori
AU  - Miyanishi M
AD  - Center for Developmental Biology, RIKEN, Kobe, Japan.
FAU - Seita, Jun
AU  - Seita J
AUID- ORCID: 0000-0002-3008-3615
AD  - AI based Healthcare and Medical Data Analysis Standardization Unit, Medical 
      Sciences Innovation Hub Program, RIKEN, Tokyo, Japan; and.
FAU - Rinkevich, Yuval
AU  - Rinkevich Y
AD  - Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz 
      Zentrum Munchen, Member of the German Center for Lung Research, Munich, Germany.
FAU - Weissman, Irving L
AU  - Weissman IL
AD  - Institute for Stem Cell Biology and Regenerative Medicine and.
AD  - Department of Developmental Biology, School of Medicine, Stanford University, 
      Stanford, CA.
LA  - eng
GR  - T32 GM007365/GM/NIGMS NIH HHS/United States
GR  - F32 HL115963/HL/NHLBI NIH HHS/United States
GR  - U01 HL099999/HL/NHLBI NIH HHS/United States
GR  - F30 DK108561/DK/NIDDK NIH HHS/United States
GR  - T32 DK098132/DK/NIDDK NIH HHS/United States
GR  - R01 HL058770/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
SB  - IM
MH  - Animals
MH  - Female
MH  - Humans
MH  - Mice
MH  - Monocytes/*metabolism
MH  - Neutrophils/*metabolism
MH  - Tissue Adhesions/*metabolism
PMC - PMC6759736
COIS- Conflict-of-interest disclosure: J.M.T., N.B.F., Y.R., R.S., M.N.M., and I.L.W. 
      have applied for patents on these topics. The remaining authors declare no 
      competing financial interests.
EDAT- 2019/09/15 06:00
MHDA- 2020/08/15 06:00
PMCR- 2019/09/13
CRDT- 2019/09/15 06:00
PHST- 2018/07/25 00:00 [received]
PHST- 2019/07/28 00:00 [accepted]
PHST- 2019/09/15 06:00 [entrez]
PHST- 2019/09/15 06:00 [pubmed]
PHST- 2020/08/15 06:00 [medline]
PHST- 2019/09/13 00:00 [pmc-release]
AID - bloodadvances.2018024026 [pii]
AID - 2018/024026 [pii]
AID - 10.1182/bloodadvances.2018024026 [doi]
PST - ppublish
SO  - Blood Adv. 2019 Sep 24;3(18):2713-2721. doi: 10.1182/bloodadvances.2018024026.