PMID- 22563471
OWN - NLM
STAT- MEDLINE
DCOM- 20120921
LR  - 20220409
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 5
DP  - 2012
TI  - Intermedin stabilized endothelial barrier function and attenuated 
      ventilator-induced lung injury in mice.
PG  - e35832
LID - 10.1371/journal.pone.0035832 [doi]
LID - e35832
AB  - BACKGROUND: Even protective ventilation may aggravate or induce lung failure, 
      particularly in preinjured lungs. Thus, new adjuvant pharmacologic strategies are 
      needed to minimize ventilator-induced lung injury (VILI). 
      Intermedin/Adrenomedullin-2 (IMD) stabilized pulmonary endothelial barrier 
      function in vitro. We hypothesized that IMD may attenuate VILI-associated lung 
      permeability in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Human pulmonary 
      microvascular endothelial cell (HPMVEC) monolayers were incubated with IMD, and 
      transcellular electrical resistance was measured to quantify endothelial barrier 
      function. Expression and localization of endogenous pulmonary IMD, and its 
      receptor complexes composed of calcitonin receptor-like receptor (CRLR) and 
      receptor activity-modifying proteins (RAMPs) 1-3 were analyzed by qRT-PCR and 
      immunofluorescence in non ventilated mouse lungs and in lungs ventilated for 6 h. 
      In untreated and IMD treated mice, lung permeability, pulmonary leukocyte 
      recruitment and cytokine levels were assessed after mechanical ventilation. 
      Further, the impact of IMD on pulmonary vasoconstriction was investigated in 
      precision cut lung slices (PCLS) and in isolated perfused and ventilated mouse 
      lungs. IMD stabilized endothelial barrier function in HPMVECs. Mechanical 
      ventilation reduced the expression of RAMP3, but not of IMD, CRLR, and RAMP1 and 
      2. Mechanical ventilation induced lung hyperpermeability, which was ameliorated 
      by IMD treatment. Oxygenation was not improved by IMD, which may be attributed to 
      impaired hypoxic vasoconstriction due to IMD treatment. IMD had minor impact on 
      pulmonary leukocyte recruitment and did not reduce cytokine levels in VILI. 
      CONCLUSIONS/SIGNIFICANCE: IMD may possibly provide a new approach to attenuate 
      VILI.
FAU - Muller-Redetzky, Holger Christian
AU  - Muller-Redetzky HC
AD  - Department of Infectious Diseases and Pulmonary Medicine, 
      Charite-Universitatsmedizin Berlin, Germany.
FAU - Kummer, Wolfgang
AU  - Kummer W
FAU - Pfeil, Uwe
AU  - Pfeil U
FAU - Hellwig, Katharina
AU  - Hellwig K
FAU - Will, Daniel
AU  - Will D
FAU - Paddenberg, Renate
AU  - Paddenberg R
FAU - Tabeling, Christoph
AU  - Tabeling C
FAU - Hippenstiel, Stefan
AU  - Hippenstiel S
FAU - Suttorp, Norbert
AU  - Suttorp N
FAU - Witzenrath, Martin
AU  - Witzenrath M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120501
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Calcitonin Receptor-Like Protein)
RN  - 0 (Peptide Hormones)
RN  - 0 (RAMP1 protein, human)
RN  - 0 (RAMP2 protein, human)
RN  - 0 (RAMP3 protein, human)
RN  - 0 (Receptor Activity-Modifying Protein 1)
RN  - 0 (Receptor Activity-Modifying Protein 2)
RN  - 0 (Receptor Activity-Modifying Protein 3)
RN  - 0 (intermedin (17-47))
SB  - IM
MH  - Animals
MH  - Calcitonin Receptor-Like Protein/genetics/metabolism
MH  - Cells, Cultured
MH  - Endothelial Cells/*drug effects/metabolism
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Hypoxia
MH  - In Vitro Techniques
MH  - Lung/blood supply/*drug effects/metabolism
MH  - Lung Injury/etiology/genetics/*prevention & control
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microvessels/cytology/drug effects/physiopathology
MH  - Peptide Hormones/genetics/metabolism/*pharmacology
MH  - Receptor Activity-Modifying Protein 1/genetics/metabolism
MH  - Receptor Activity-Modifying Protein 2/genetics/metabolism
MH  - Receptor Activity-Modifying Protein 3/genetics/metabolism
MH  - Respiration, Artificial/adverse effects
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Vasoconstriction/drug effects
PMC - PMC3341380
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/05/09 06:00
MHDA- 2012/09/22 06:00
PMCR- 2012/05/01
CRDT- 2012/05/08 06:00
PHST- 2011/09/14 00:00 [received]
PHST- 2012/03/22 00:00 [accepted]
PHST- 2012/05/08 06:00 [entrez]
PHST- 2012/05/09 06:00 [pubmed]
PHST- 2012/09/22 06:00 [medline]
PHST- 2012/05/01 00:00 [pmc-release]
AID - PONE-D-11-17951 [pii]
AID - 10.1371/journal.pone.0035832 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(5):e35832. doi: 10.1371/journal.pone.0035832. Epub 2012 May 1.