PMID- 21143965
OWN - NLM
STAT- MEDLINE
DCOM- 20120126
LR  - 20211020
IS  - 1466-609X (Electronic)
IS  - 1364-8535 (Print)
IS  - 1364-8535 (Linking)
VI  - 14
IP  - 6
DP  - 2010
TI  - Inhibition of lectin-like oxidized low-density lipoprotein receptor-1 reduces 
      leukocyte adhesion within the intestinal microcirculation in experimental 
      endotoxemia in rats.
PG  - R223
LID - 10.1186/cc9367 [doi]
AB  - INTRODUCTION: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), 
      the major endothelial receptor for oxidized low-density lipoprotein, is also 
      involved in leukocyte recruitment. Systemic leukocyte activation in sepsis 
      represents a crucial factor in the impairment of the microcirculation of 
      different tissues, causing multiple organ failure and subsequently death. The aim 
      of our experimental study was to evaluate the effects of LOX-1 inhibition on the 
      endotoxin-induced leukocyte adherence and capillary perfusion within the 
      intestinal microcirculation by using intravital microscopy (IVM). METHODS: We 
      used 40 male Lewis rats for the experiments. Ten placebo-treated animals served 
      as a control. Thirty animals received 5 mg/kg lipopolysaccharide (LPS) 
      intravenously. Ten endotoxemic rats remained untreated. In 10 LPS animals, we 
      administered additionally 10 mg/kg LOX-1 antibodies. Ten further LPS animals 
      received a nonspecific immunoglobulin (rat IgG) intravenously. After 2 hours of 
      observation, intestinal microcirculation was evaluated by using IVM; the plasma 
      levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis 
      factor-alpha (TNF-alpha) were determined; and LOX-1 expression was quantified in 
      intestinal tissue with Western blot and reverse-transcription polymerase chain 
      reaction (PCR). RESULTS: LOX-1 inhibition significantly reduced LPS-induced 
      leukocyte adhesion in intestinal submucosal venules (P < 0.05). At the protein 
      and mRNA levels, LOX-1 expression was significantly increased in untreated LPS 
      animals (P < 0.05), whereas in animals treated with LOX-1 antibody, expression of 
      LOX-1 was reduced (P < 0.05). MCP-1 plasma level was reduced after LOX-1 antibody 
      administration. CONCLUSIONS: Inhibition of LOX-1 reduced leukocyte activation in 
      experimental endotoxemia. LOX-1 represents a novel target for the modulation of 
      the inflammatory response within the microcirculation in sepsis.
FAU - Landsberger, Martin
AU  - Landsberger M
AD  - Department of Internal Medicine B, University Hospital Greifswald, 
      Friedrich-Loeffler-Strasse 23 a, D-17475 Greifswald, Germany.
FAU - Zhou, Juan
AU  - Zhou J
FAU - Wilk, Sebastian
AU  - Wilk S
FAU - Thaumuller, Corinna
AU  - Thaumuller C
FAU - Pavlovic, Dragan
AU  - Pavlovic D
FAU - Otto, Marion
AU  - Otto M
FAU - Whynot, Sara
AU  - Whynot S
FAU - Hung, Orlando
AU  - Hung O
FAU - Murphy, Michael F
AU  - Murphy MF
FAU - Cerny, Vladimir
AU  - Cerny V
FAU - Felix, Stephan B
AU  - Felix SB
FAU - Lehmann, Christian
AU  - Lehmann C
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101210
PL  - England
TA  - Crit Care
JT  - Critical care (London, England)
JID - 9801902
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Scavenger Receptors, Class E)
SB  - IM
MH  - Animals
MH  - Antibodies, Bacterial/pharmacology/*therapeutic use
MH  - Cell Adhesion/immunology
MH  - Endotoxemia/immunology/*pathology
MH  - Intestinal Mucosa/*blood supply/immunology/*pathology
MH  - Leukocytes/*immunology/pathology
MH  - Male
MH  - Microcirculation/*immunology
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Scavenger Receptors, Class E/*antagonists & inhibitors/immunology
PMC - PMC3220004
EDAT- 2010/12/15 06:00
MHDA- 2012/01/27 06:00
PMCR- 2010/12/10
CRDT- 2010/12/15 06:00
PHST- 2010/04/30 00:00 [received]
PHST- 2010/08/03 00:00 [revised]
PHST- 2010/12/10 00:00 [accepted]
PHST- 2010/12/15 06:00 [entrez]
PHST- 2010/12/15 06:00 [pubmed]
PHST- 2012/01/27 06:00 [medline]
PHST- 2010/12/10 00:00 [pmc-release]
AID - cc9367 [pii]
AID - 10.1186/cc9367 [doi]
PST - ppublish
SO  - Crit Care. 2010;14(6):R223. doi: 10.1186/cc9367. Epub 2010 Dec 10.