PMID- 22610172
OWN - NLM
STAT- MEDLINE
DCOM- 20121009
LR  - 20211021
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 303
IP  - 2
DP  - 2012 Jul 15
TI  - Dexamethasone blocks the systemic inflammation of alveolar hypoxia at several 
      sites in the inflammatory cascade.
PG  - H168-77
LID - 10.1152/ajpheart.00106.2012 [doi]
AB  - Alveolar hypoxia produces a rapid and widespread systemic inflammation in rats. 
      The inflammation is initiated by the release into the circulation of monocyte 
      chemoattractant protein-1 (MCP-1) from alveolar macrophages (AMO) activated by 
      the low alveolar Po(2). Circulating MCP-1 induces mast cell (MC) degranulation 
      with renin release and activation of the local renin-angiotensin system, leading 
      to microvascular leukocyte recruitment and increased vascular permeability. We 
      investigated the effect of dexamethasone, a synthetic anti-inflammatory 
      glucocorticoid, on the development of the systemic inflammation of alveolar 
      hypoxia and its site(s) of action in the inflammatory cascade. The inflammatory 
      steps investigated were the activation of primary cultures of AMO by hypoxia, the 
      degranulation of MCs by MCP-1 in the mesentery microcirculation of rats, and the 
      effect of angiotensin II (ANG II) on the leukocyte/endothelial interface of the 
      mesentery microcirculation. Dexamethasone prevented the mesentery inflammation in 
      conscious rats breathing 10% O(2) for 4 h by acting in all key steps of the 
      inflammatory cascade. Dexamethasone: 1) blocked the hypoxia-induced AMO 
      activation and the release of MCP-1 and abolished the increase in plasma MCP-1 of 
      conscious, hypoxic rats; 2) prevented the MCP-1-induced degranulation of 
      mesentery perivascular MCs and reduced the number of peritoneal MCs, and 3) 
      blocked the leukocyte-endothelial adherence and the extravasation of albumin 
      induced by topical ANG II in the mesentery. The effect at each site was 
      sufficient to prevent the AMO-initiated inflammation of hypoxia. These results 
      may explain the effectiveness of dexamethasone in the treatment of the systemic 
      effects of alveolar hypoxia.
FAU - Chao, Jie
AU  - Chao J
AD  - Department of Molecular and Integrative Physiology, University of Kansas Medical 
      Center, Kansas City, KA 66160, USA.
FAU - Viets, Zachary
AU  - Viets Z
FAU - Donham, Paula
AU  - Donham P
FAU - Wood, John G
AU  - Wood JG
FAU - Gonzalez, Norberto C
AU  - Gonzalez NC
LA  - eng
GR  - R01 HL-39443/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120518
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 11128-99-7 (Angiotensin II)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Angiotensin II/pharmacology
MH  - Animals
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Cell Degranulation/drug effects/physiology
MH  - Cells, Cultured
MH  - Chemokine CCL2/blood/metabolism
MH  - Dexamethasone/*therapeutic use
MH  - Hypoxia/*physiopathology
MH  - Inflammation/*drug therapy
MH  - Macrophages, Alveolar/drug effects
MH  - Male
MH  - Mast Cells/drug effects
MH  - Mesentery/drug effects/physiopathology
MH  - Pulmonary Alveoli/drug effects/physiopathology
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC3404698
EDAT- 2012/05/23 06:00
MHDA- 2012/10/10 06:00
PMCR- 2013/07/15
CRDT- 2012/05/22 06:00
PHST- 2012/05/22 06:00 [entrez]
PHST- 2012/05/23 06:00 [pubmed]
PHST- 2012/10/10 06:00 [medline]
PHST- 2013/07/15 00:00 [pmc-release]
AID - ajpheart.00106.2012 [pii]
AID - H-00106-2012 [pii]
AID - 10.1152/ajpheart.00106.2012 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2012 Jul 15;303(2):H168-77. doi: 
      10.1152/ajpheart.00106.2012. Epub 2012 May 18.