PMID- 11839548
OWN - NLM
STAT- MEDLINE
DCOM- 20020307
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 282
IP  - 3
DP  - 2002 Mar
TI  - IL-13-dependent autocrine signaling mediates altered responsiveness of 
      IgE-sensitized airway smooth muscle.
PG  - L520-8
AB  - In testing the hypothesis that interleukin-4 receptor alpha-subunit (IL-4R 
      alpha)-coupled signaling mediates altered airway smooth muscle (ASM) 
      responsiveness in the atopic sensitized state, isolated rabbit tracheal ASM 
      segments were passively sensitized with immunoglobulin E (IgE) immune complexes, 
      both in the absence and presence of an IL-4R alpha blocking antibody (anti-IL-4R 
      alpha Ab). Relative to control ASM, IgE-sensitized tissues exhibited enhanced 
      isometric constrictor responses to administered ACh and attenuated relaxation 
      responses to isoproterenol. These proasthmatic-like effects were prevented in 
      IgE-sensitized ASM that were pretreated with anti-IL-4R alpha Ab. In 
      complementary experiments, IgE-sensitized cultured human ASM cells exhibited 
      upregulated expression of IL-13 mRNA and protein, whereas IL-4 expression was 
      undetected. Moreover, extended studies demonstrated that 1) exogenous IL-13 
      administration to naive ASM elicited augmented contractility to ACh and impaired 
      relaxation to isoproterenol, 2) these effects of IL-13 were prevented by 
      pretreating the tissues with an IL-5 receptor blocking antibody, and 3) IL-13 
      administration induced upregulated mRNA expression and release of IL-5 protein 
      from cultured ASM cells. Collectively, these findings provide new evidence 
      demonstrating that the altered responsiveness of IgE-sensitized ASM is largely 
      attributed to activation of an intrinsic Th2-type autocrine mechanism involving 
      IL-13/IL-4R alpha-coupled release and action of IL-5 in the sensitized ASM 
      itself.
FAU - Grunstein, M M
AU  - Grunstein MM
AD  - Division of Pulmonary Medicine, Joseph Stokes, Jr. Research Institute, The 
      Children's Hospital of Philadelphia, University of Pennsylvania School of 
      Medicine, Philadelphia, Pennsylvania 19104, USA. grunstein@email.chop.edu
FAU - Hakonarson, H
AU  - Hakonarson H
FAU - Leiter, J
AU  - Leiter J
FAU - Chen, M
AU  - Chen M
FAU - Whelan, R
AU  - Whelan R
FAU - Grunstein, J S
AU  - Grunstein JS
FAU - Chuang, S
AU  - Chuang S
LA  - eng
GR  - HL-31467/HL/NHLBI NIH HHS/United States
GR  - HL-58245/HL/NHLBI NIH HHS/United States
GR  - HL-59906/HL/NHLBI NIH HHS/United States
GR  - HL-61038/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Cholinergic Agents)
RN  - 0 (Interleukin-13)
RN  - 0 (Interleukin-5)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Interleukin-4)
RN  - 207137-56-2 (Interleukin-4)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
CIN - Am J Physiol Lung Cell Mol Physiol. 2002 Mar;282(3):L518-9. PMID: 11839547
MH  - Acetylcholine/pharmacology
MH  - Animals
MH  - Autocrine Communication/*physiology
MH  - Cholinergic Agents/pharmacology
MH  - Humans
MH  - Immunization
MH  - Immunoglobulin E/*immunology
MH  - In Vitro Techniques
MH  - Interleukin-13/pharmacology/*physiology
MH  - Interleukin-4/metabolism
MH  - Interleukin-5/genetics/metabolism/physiology
MH  - Muscle, Smooth/immunology/*physiology
MH  - Protein Isoforms/physiology
MH  - RNA, Messenger/metabolism
MH  - Rabbits
MH  - Receptors, Interleukin-4/physiology
MH  - Signal Transduction/*physiology
MH  - Trachea/immunology/*physiology
EDAT- 2002/02/13 10:00
MHDA- 2002/03/08 10:01
CRDT- 2002/02/13 10:00
PHST- 2002/02/13 10:00 [pubmed]
PHST- 2002/03/08 10:01 [medline]
PHST- 2002/02/13 10:00 [entrez]
AID - 10.1152/ajplung.00343.2001 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2002 Mar;282(3):L520-8. doi: 
      10.1152/ajplung.00343.2001.