PMID- 21963836
OWN - NLM
STAT- MEDLINE
DCOM- 20120123
LR  - 20211020
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 301
IP  - 6
DP  - 2011 Dec
TI  - Renin released from mast cells activated by circulating MCP-1 initiates the 
      microvascular phase of the systemic inflammation of alveolar hypoxia.
PG  - H2264-70
LID - 10.1152/ajpheart.00461.2011 [doi]
AB  - Reduced alveolar Po(2) in rats produces a rapid systemic inflammation 
      characterized by reactive O(2) species generation, mast cell (MC) degranulation, 
      leukocyte-endothelial interactions, and increased vascular permeability. The 
      inflammation is not initiated by the low systemic Po(2) but rather by the release 
      of monocyte chemoattractant protein-1 (MCP-1) from alveolar macrophages (AMO) 
      activated by alveolar hypoxia. Circulating AMO-borne MCP-1 induces MC 
      degranulation, which activates the local renin-angiotensin system (RAS) and 
      mediates the microvascular inflammation. This study was directed to determine the 
      mechanism of RAS activation by MCP-1-induced MC degranulation. Experiments in 
      isolated rat peritoneal MCs showed the following: 1) Western blots and 
      immunocytochemistry demonstrated the presence of renin and angiotensin-converting 
      enzyme (ACE) in MCs and their release upon degranulation; 2) MCP-1-induced 
      degranulation of MCs incubated in plasma produced an increase in angiotensin II 
      (ANG II) concentration; and 3) this increase was inhibited completely by the 
      following agents: the MCP-1 receptor antagonist RS-102895, the specific rat renin 
      inhibitor WFML, or the ACE inhibitor captopril administered separately. Captopril 
      also inhibited ANG II generation by MCs incubated in culture medium plus ANG I. 
      The results show that peritoneal MCs contain active renin, which activates the 
      RAS upon degranulation, and that peritoneal MCs are a source of ACE and suggest 
      that conversion of ANG I to ANG II is mediated predominantly by ACE. This study 
      provides novel evidence of the presence of active renin in rat peritoneal MCs and 
      helps explain the mechanism of activation of the RAS during alveolar hypoxia.
FAU - Chao, Jie
AU  - Chao J
AD  - Department of Molecular and Integrative Physiology, University of Kansas Medical 
      Center, Kansas City, 66160, USA.
FAU - Blanco, Gustavo
AU  - Blanco G
FAU - Wood, John G
AU  - Wood JG
FAU - Gonzalez, Norberto C
AU  - Gonzalez NC
LA  - eng
GR  - HL-R01-39443/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 - 20110930
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Ccr2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - 11128-99-7 (Angiotensin II)
RN  - 9041-90-1 (Angiotensin I)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
RN  - EC 3.4.23.15 (Renin)
SB  - IM
MH  - Angiotensin I/metabolism
MH  - Angiotensin II/metabolism
MH  - Angiotensin-Converting Enzyme Inhibitors/pharmacology
MH  - Animals
MH  - Blotting, Western
MH  - *Cell Degranulation/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Hypoxia/*complications/immunology/metabolism
MH  - Immunohistochemistry
MH  - Inflammation/*etiology/immunology/metabolism/prevention & control
MH  - *Macrophage Activation/drug effects
MH  - Macrophages, Peritoneal/drug effects/immunology/*metabolism
MH  - Peptidyl-Dipeptidase A/metabolism
MH  - Pulmonary Alveoli/immunology/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, CCR2/antagonists & inhibitors/metabolism
MH  - Renin/antagonists & inhibitors/*metabolism
MH  - Renin-Angiotensin System/drug effects
PMC - PMC3233815
EDAT- 2011/10/04 06:00
MHDA- 2012/01/24 06:00
PMCR- 2012/12/01
CRDT- 2011/10/04 06:00
PHST- 2011/10/04 06:00 [entrez]
PHST- 2011/10/04 06:00 [pubmed]
PHST- 2012/01/24 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - ajpheart.00461.2011 [pii]
AID - H-00461-2011 [pii]
AID - 10.1152/ajpheart.00461.2011 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2011 Dec;301(6):H2264-70. doi: 
      10.1152/ajpheart.00461.2011. Epub 2011 Sep 30.