PMID- 33124967
OWN - NLM
STAT- MEDLINE
DCOM- 20210826
LR  - 20240330
IS  - 2162-1918 (Print)
IS  - 2162-1934 (Electronic)
IS  - 2162-1918 (Linking)
VI  - 9
IP  - 12
DP  - 2020 Dec
TI  - Systemic Delivery of Anti-Integrin alphaL Antibodies Reduces Early Macrophage 
      Recruitment, Inflammation, and Scar Formation in Murine Burn Wounds.
PG  - 637-648
LID - 10.1089/wound.2019.1035 [doi]
AB  - Objective: Increased macrophage recruitment in the early stages of wound healing 
      leads to an excessive inflammatory response associated with elevated fibrosis and 
      scarring. This recruitment relies upon integrins on the surface of monocytes that 
      regulate their migration and extravasation from the circulation into the wound 
      site, where they differentiate into macrophages. The aim of this study was to 
      determine if inhibiting monocyte extravasation from the circulation into burns 
      would reduce macrophages numbers in burns and lead to reduced inflammation and 
      scar formation. Approach: Scald burns were created on mice and treated with 
      integrin alpha L (alphaL) function blocking antibody via intravenous delivery day 1 
      after injury. The effect of inhibiting macrophage recruitment into the burn was 
      assessed using macro- and microscopic wound parameters as well as 
      immunohistochemistry for inflammatory cell markers, cytokines, and collagen 
      deposition. Results: Burn wound-associated macrophages were reduced by 54.7% at 
      day 3 following treatment with integrin alphaL antibody, with levels returning to 
      normal by day 7. This reduction in macrophages led to a concomitant reduction in 
      inflammatory mediators, including tumor necrosis factor-alpha (TNFalpha) and Il-10 as 
      well as a reduction in proscarring transforming growth factor beta 1 (TGFbeta1). 
      This reduced inflammatory response was also associated with less alpha smooth 
      muscle actin (alphaSMA) expression and an overall trend toward reduced scar formation 
      with a lower collagen I/III ratio. Innovation: Treatment of burns with integrin 
      alphaL function blocking antibodies reduces inflammation in burn wounds. Conclusion: 
      These results suggest that reducing macrophage infiltration into burn wounds may 
      lead to a reduced early inflammatory response and less scar formation following 
      burn injury.
FAU - Strudwick, Xanthe L
AU  - Strudwick XL
AD  - Future Industries Institute, University of South Australia, Adelaide, South 
      Australia, Australia.
FAU - Adams, Damian H
AU  - Adams DH
AD  - Future Industries Institute, University of South Australia, Adelaide, South 
      Australia, Australia.
FAU - Pyne, Natasha T
AU  - Pyne NT
AD  - Centre for Cancer Biology, University of South Australia, Adelaide, South 
      Australia, Australia.
FAU - Samuel, Michael S
AU  - Samuel MS
AD  - Centre for Cancer Biology, University of South Australia, Adelaide, South 
      Australia, Australia.
AD  - Faculty of Health and Medical Sciences, School of Medicine, University of 
      Adelaide, Adelaide, South Australia, Australia.
FAU - Murray, Rachael Z
AU  - Murray RZ
AD  - Institute of Health and Biomedical Innovation, Queensland University of 
      Technology, Brisbane, Queensland, Australia.
FAU - Cowin, Allison J
AU  - Cowin AJ
AD  - Future Industries Institute, University of South Australia, Adelaide, South 
      Australia, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200128
PL  - United States
TA  - Adv Wound Care (New Rochelle)
JT  - Advances in wound care
JID - 101590593
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (CD11a Antigen)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*pharmacology
MH  - Burns/*drug therapy/pathology
MH  - CD11a Antigen/*immunology
MH  - Cicatrix/prevention & control
MH  - Collagen/drug effects/metabolism
MH  - Fibrosis/drug therapy
MH  - Humans
MH  - Inflammation/prevention & control
MH  - Inflammation Mediators
MH  - Macrophages/*drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Transforming Growth Factor beta1/drug effects/metabolism
MH  - Tumor Necrosis Factor-alpha/drug effects/metabolism
MH  - Wound Healing/*drug effects
PMC - PMC7698651
OTO - NOTNLM
OT  - TGFbeta1
OT  - TNFalpha
OT  - burns
OT  - integrin
OT  - macrophage
COIS- No competing financial interests exist. The content of this article was expressly 
      written by the author(s) listed. No ghostwriters were used to write this article.
EDAT- 2020/10/31 06:00
MHDA- 2021/08/27 06:00
PMCR- 2021/12/01
CRDT- 2020/10/30 12:09
PHST- 2020/10/30 12:09 [entrez]
PHST- 2020/10/31 06:00 [pubmed]
PHST- 2021/08/27 06:00 [medline]
PHST- 2021/12/01 00:00 [pmc-release]
AID - 10.1089/wound.2019.1035 [pii]
AID - 10.1089/wound.2019.1035 [doi]
PST - ppublish
SO  - Adv Wound Care (New Rochelle). 2020 Dec;9(12):637-648. doi: 
      10.1089/wound.2019.1035. Epub 2020 Jan 28.