PMID- 24689549
OWN - NLM
STAT- MEDLINE
DCOM- 20141219
LR  - 20211021
IS  - 1530-0277 (Electronic)
IS  - 0145-6008 (Print)
IS  - 0145-6008 (Linking)
VI  - 38
IP  - 5
DP  - 2014 May
TI  - Episodic binge ethanol exposure impairs murine macrophage infiltration and delays 
      wound closure by promoting defects in early innate immune responses.
PG  - 1347-55
LID - 10.1111/acer.12369 [doi]
AB  - BACKGROUND: Exacerbation of cutaneous wound infections and delayed wound closure 
      are frequent complications seen in alcohol exposed subjects who sustain injuries. 
      We previously reported that acute alcohol exposure alters the early dermal 
      inflammatory phase of wound healing and also several parameters of the 
      proliferative wound healing phase in wounds from ethanol (EtOH)-treated mice for 
      several days or weeks after EtOH exposure. Hence, it is likely that the 
      cumulative defects arising in the early phases of the wound healing process 
      directly contribute to the increased complications observed in intoxicated 
      patients at the time of injury. METHODS: C57BL/6 mice were given intraperitoneal 
      EtOH (2.2 g/kg body weight) or vehicle (saline) EtOH using our episodic binge 
      EtOH exposure protocol (3 days EtOH, 4 days off, 3 days EtOH) to yield a blood 
      alcohol concentration (BAC) of 300 mg/dl at the time of wounding. Mice were 
      subjected to six 3 mm full-thickness dorsal wounds and immediately treated 
      topically with 10 mul of sterile saline (control) or diluted Staphylococcus aureus 
      corresponding to 1 x 10(4) CFU/wound. Wounds were harvested at 24 hours post 
      injury to evaluate wound area, neutrophil and macrophage accumulation, and the 
      protein levels of cytokines, interleukin-6 (IL-6), IL-1beta, and IL-10, and 
      chemokines, macrophage inflammatory protein-2 (MIP-2) and MIP-1alpha, monocyte 
      chemotactic protein-1 (MCP-1), and keratinocyte-derived chemokine (KC). The 
      abundance and localization of cathelicidin-related antimicrobial peptide (CRAMP) 
      and the kallikrein epidermal proteases (KLK5 and KLK7) were also determined. 
      RESULTS: Compared to control mice, EtOH-treated mice exhibited delayed wound 
      closure, decreased macrophage accumulation, and impaired production of MIP-1alpha. 
      Furthermore, skin from EtOH-treated mice demonstrated a reduction in the 
      abundance of epidermal CRAMP and KLK7. CONCLUSIONS: These findings suggest that 
      EtOH exposure hinders several distinct components of the innate immune response, 
      including phagocyte recruitment and chemokine/cytokine and AMP production. 
      Together, these effects likely contribute to delayed wound closure and enhanced 
      infection severity observed in intoxicated patients.
CI  - Copyright (c) 2014 by the Research Society on Alcoholism.
FAU - Curtis, Brenda J
AU  - Curtis BJ
AD  - Health Sciences Division , Alcohol Research Program, The Burn and Shock Trauma 
      Research Institute, Loyola University Chicago, Maywood, Illinois; Health Sciences 
      Division , Department of Surgery, The Burn and Shock Trauma Research Institute, 
      Loyola University Chicago, Maywood, Illinois.
FAU - Hlavin, Sara
AU  - Hlavin S
FAU - Brubaker, Aleah L
AU  - Brubaker AL
FAU - Kovacs, Elizabeth J
AU  - Kovacs EJ
FAU - Radek, Katherine A
AU  - Radek KA
LA  - eng
GR  - F32 AA021636/AA/NIAAA NIH HHS/United States
GR  - T32 AA013527/AA/NIAAA NIH HHS/United States
GR  - P30AA19373/AA/NIAAA NIH HHS/United States
GR  - F32AA021636/AA/NIAAA NIH HHS/United States
GR  - P30 AA019373/AA/NIAAA NIH HHS/United States
GR  - R01 AA012034/AA/NIAAA NIH HHS/United States
GR  - T32AA013527/AA/NIAAA NIH HHS/United States
GR  - R01AA012034/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140401
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Animals
MH  - Ethanol/administration & dosage/*pharmacology
MH  - Fluorescent Antibody Technique
MH  - Immunity, Innate/*drug effects
MH  - Macrophages/*drug effects
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Wound Healing/*drug effects
PMC - PMC4001884
MID - NIHMS557421
OTO - NOTNLM
OT  - Antimicrobial Peptides
OT  - Cathelicidin
OT  - Inflammation
OT  - Macrophages
OT  - Proteases
OT  - Wound Healing
EDAT- 2014/04/03 06:00
MHDA- 2014/12/20 06:00
PMCR- 2015/05/01
CRDT- 2014/04/03 06:00
PHST- 2013/03/28 00:00 [received]
PHST- 2013/12/23 00:00 [accepted]
PHST- 2014/04/03 06:00 [entrez]
PHST- 2014/04/03 06:00 [pubmed]
PHST- 2014/12/20 06:00 [medline]
PHST- 2015/05/01 00:00 [pmc-release]
AID - 10.1111/acer.12369 [doi]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2014 May;38(5):1347-55. doi: 10.1111/acer.12369. Epub 2014 
      Apr 1.