PMID- 18202178
OWN - NLM
STAT- MEDLINE
DCOM- 20080225
LR  - 20240316
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 105
IP  - 4
DP  - 2008 Jan 29
TI  - Mast cell renin and a local renin-angiotensin system in the airway: role in 
      bronchoconstriction.
PG  - 1315-20
LID - 10.1073/pnas.0709739105 [doi]
AB  - We previously reported that mast cells express renin, the rate-limiting enzyme in 
      the renin-angiotensin cascade. We have now assessed whether mast cell renin 
      release triggers angiotensin formation in the airway. In isolated rat bronchial 
      rings, mast cell degranulation released enzyme with angiotensin I-forming 
      activity blocked by the selective renin inhibitor BILA2157. Local generation of 
      angiotensin (ANG II) from mast cell renin elicited bronchial smooth muscle 
      contraction mediated by ANG II type 1 receptors (AT(1)R). In a guinea pig model 
      of immediate type hypersensitivity, anaphylactic mast cell degranulation in 
      bronchial rings resulted in ANG II-mediated constriction. As in rat bronchial 
      rings, bronchoconstriction (BC) was inhibited by a renin inhibitor, an AT(1)R 
      blocker, and a mast cell stabilizer. Anaphylactic release of renin, histamine, 
      and beta-hexosaminidase from mast cells was confirmed in the effluent from 
      isolated, perfused guinea pig lung. To relate the significance of this finding to 
      humans, mast cells were isolated from macroscopically normal human lung waste 
      tissue specimens. Sequence analysis of human lung mast cell RNA showed 100% 
      homology between human lung mast cell renin and kidney renin between exons 1 and 
      10. Furthermore, the renin protein expressed in lung mast cells was enzymatically 
      active. Our results demonstrate the existence of an airway renin-angiotensin 
      system triggered by release of mast-cell renin. The data show that locally 
      produced ANG II is a critical factor governing BC, opening the possibility for 
      novel therapeutic targets in the management of airway disease.
FAU - Veerappan, Arul
AU  - Veerappan A
AD  - Department of Physiology and Biophysics, Weill Cornell Medical College, 1300 York 
      Avenue, New York, NY 10065, USA.
FAU - Reid, Alicia C
AU  - Reid AC
FAU - Estephan, Racha
AU  - Estephan R
FAU - O'Connor, Nathan
AU  - O'Connor N
FAU - Thadani-Mulero, Maria
AU  - Thadani-Mulero M
FAU - Salazar-Rodriguez, Mariselis
AU  - Salazar-Rodriguez M
FAU - Levi, Roberto
AU  - Levi R
FAU - Silver, Randi B
AU  - Silver RB
LA  - eng
GR  - P01 HL046403/HL/NHLBI NIH HHS/United States
GR  - HL46403/HL/NHLBI NIH HHS/United States
GR  - R01 DK060726/DK/NIDDK NIH HHS/United States
GR  - R01 HL047073/HL/NHLBI NIH HHS/United States
GR  - HL73400/HL/NHLBI NIH HHS/United States
GR  - R01 HL034215/HL/NHLBI NIH HHS/United States
GR  - R01 HL073400/HL/NHLBI NIH HHS/United States
GR  - HL47073/HL/NHLBI NIH HHS/United States
GR  - R37 HL047073/HL/NHLBI NIH HHS/United States
GR  - HL34215/HL/NHLBI NIH HHS/United States
GR  - DK60726/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080117
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 3.4.23.15 (Renin)
SB  - IM
MH  - Angiotensin II/biosynthesis/physiology
MH  - Animals
MH  - Bronchi/*enzymology/metabolism/physiology
MH  - Bronchoconstriction/*physiology
MH  - Cell Degranulation/physiology
MH  - Guinea Pigs
MH  - Humans
MH  - Lung/enzymology/metabolism/physiology
MH  - Male
MH  - Mast Cells/*enzymology/metabolism/physiology
MH  - Muscle Contraction/physiology
MH  - Muscle, Smooth/cytology/metabolism/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Angiotensin, Type 1/metabolism
MH  - Renin/chemistry/genetics/*metabolism/physiology
MH  - Renin-Angiotensin System/*physiology
PMC - PMC2234135
COIS- Conflict of interest statement: A patent for related technology has been filed 
      with the U.S. Patent and Trademark office by Cornell University. R.B.S. and R.L. 
      are coinventors.
EDAT- 2008/01/19 09:00
MHDA- 2008/02/26 09:00
PMCR- 2008/01/29
CRDT- 2008/01/19 09:00
PHST- 2008/01/19 09:00 [pubmed]
PHST- 2008/02/26 09:00 [medline]
PHST- 2008/01/19 09:00 [entrez]
PHST- 2008/01/29 00:00 [pmc-release]
AID - 0709739105 [pii]
AID - 9027 [pii]
AID - 10.1073/pnas.0709739105 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1315-20. doi: 
      10.1073/pnas.0709739105. Epub 2008 Jan 17.