IL-4 increases surfactant and regulates metabolism in vivo

Machiko Ikegami, Jeffrey A. Whitsett, Zissis Chroneos, Gary F. Ross, Jacquelyn A. Reed, Cindy J. Bachurski, Alan H. Jobe

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Mice that express interleukin (IL)-4 in Clara cells (CCSP-IL-4) develop chronic airway inflammation and an alveolar proteinosis-like syndrome. To identify the role of IL-4 in surfactant homeostasis, we measured lipid and protein metabolism in the lungs of CCSP-IL-4 mice in vivo. Alveolar saturated phosphatidylcholine (Sat PC) pools were increased 6.5-fold and lung tissue Sat PC pools were increased 4.8-fold in the IL-4 transgenic mice. Whereas surfactant protein (SP) A was increased proportionately to Sat PC, SP-D was increased approximately 90-fold in the IL-4 mice compared with wild-type mice and was associated with 2.8-fold increase in SP-D mRNA. The incorporation of palmitate and choline into Sat PC was increased about twofold in CCSP-IL-4 mice. Although trace doses of radiolabeled Sat PC were cleared from the air spaces and lungs of CCSP-IL-4 mice more slowly than in wild-type mice, net clearance of Sat PC from the lungs of CCSP-IL-4 mice was sixfold higher in the IL-4 mice than in wild-type mice because of the larger Sat PC pool sizes. Expression of IL-4 in Clara cells increased surfactant lipid synthesis and clearance, establishing a new equilibrium with increased surfactant pools and an alveolar proteinosis associated with a selective increase in SP-D protein, demonstrating a previously unexpected effect of IL-4 in pulmonary surfactant homeostasis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume278
Issue number1 22-1
StatePublished - Jan 1 2000

Fingerprint

Surface-Active Agents
Interleukin-4
Phosphatidylcholines
Pulmonary Surfactant-Associated Protein D
Lung
Homeostasis
Pulmonary Surfactant-Associated Protein A
Pulmonary Surfactants
Palmitates
Choline
Lipid Metabolism
Transgenic Mice
Proteins
Air
Inflammation
Lipids
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Ikegami, M., Whitsett, J. A., Chroneos, Z., Ross, G. F., Reed, J. A., Bachurski, C. J., & Jobe, A. H. (2000). IL-4 increases surfactant and regulates metabolism in vivo. American Journal of Physiology - Lung Cellular and Molecular Physiology, 278(1 22-1).
Ikegami, Machiko ; Whitsett, Jeffrey A. ; Chroneos, Zissis ; Ross, Gary F. ; Reed, Jacquelyn A. ; Bachurski, Cindy J. ; Jobe, Alan H. / IL-4 increases surfactant and regulates metabolism in vivo. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2000 ; Vol. 278, No. 1 22-1.
@article{7835257b8048427bb3d185d3444a604c,
title = "IL-4 increases surfactant and regulates metabolism in vivo",
abstract = "Mice that express interleukin (IL)-4 in Clara cells (CCSP-IL-4) develop chronic airway inflammation and an alveolar proteinosis-like syndrome. To identify the role of IL-4 in surfactant homeostasis, we measured lipid and protein metabolism in the lungs of CCSP-IL-4 mice in vivo. Alveolar saturated phosphatidylcholine (Sat PC) pools were increased 6.5-fold and lung tissue Sat PC pools were increased 4.8-fold in the IL-4 transgenic mice. Whereas surfactant protein (SP) A was increased proportionately to Sat PC, SP-D was increased approximately 90-fold in the IL-4 mice compared with wild-type mice and was associated with 2.8-fold increase in SP-D mRNA. The incorporation of palmitate and choline into Sat PC was increased about twofold in CCSP-IL-4 mice. Although trace doses of radiolabeled Sat PC were cleared from the air spaces and lungs of CCSP-IL-4 mice more slowly than in wild-type mice, net clearance of Sat PC from the lungs of CCSP-IL-4 mice was sixfold higher in the IL-4 mice than in wild-type mice because of the larger Sat PC pool sizes. Expression of IL-4 in Clara cells increased surfactant lipid synthesis and clearance, establishing a new equilibrium with increased surfactant pools and an alveolar proteinosis associated with a selective increase in SP-D protein, demonstrating a previously unexpected effect of IL-4 in pulmonary surfactant homeostasis.",
author = "Machiko Ikegami and Whitsett, {Jeffrey A.} and Zissis Chroneos and Ross, {Gary F.} and Reed, {Jacquelyn A.} and Bachurski, {Cindy J.} and Jobe, {Alan H.}",
year = "2000",
month = "1",
day = "1",
language = "English (US)",
volume = "278",
journal = "American Journal of Physiology",
issn = "1040-0605",
publisher = "American Physiological Society",
number = "1 22-1",

}

Ikegami, M, Whitsett, JA, Chroneos, Z, Ross, GF, Reed, JA, Bachurski, CJ & Jobe, AH 2000, 'IL-4 increases surfactant and regulates metabolism in vivo', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 278, no. 1 22-1.

IL-4 increases surfactant and regulates metabolism in vivo. / Ikegami, Machiko; Whitsett, Jeffrey A.; Chroneos, Zissis; Ross, Gary F.; Reed, Jacquelyn A.; Bachurski, Cindy J.; Jobe, Alan H.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 278, No. 1 22-1, 01.01.2000.

Research output: Contribution to journalArticle

TY - JOUR

T1 - IL-4 increases surfactant and regulates metabolism in vivo

AU - Ikegami, Machiko

AU - Whitsett, Jeffrey A.

AU - Chroneos, Zissis

AU - Ross, Gary F.

AU - Reed, Jacquelyn A.

AU - Bachurski, Cindy J.

AU - Jobe, Alan H.

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Mice that express interleukin (IL)-4 in Clara cells (CCSP-IL-4) develop chronic airway inflammation and an alveolar proteinosis-like syndrome. To identify the role of IL-4 in surfactant homeostasis, we measured lipid and protein metabolism in the lungs of CCSP-IL-4 mice in vivo. Alveolar saturated phosphatidylcholine (Sat PC) pools were increased 6.5-fold and lung tissue Sat PC pools were increased 4.8-fold in the IL-4 transgenic mice. Whereas surfactant protein (SP) A was increased proportionately to Sat PC, SP-D was increased approximately 90-fold in the IL-4 mice compared with wild-type mice and was associated with 2.8-fold increase in SP-D mRNA. The incorporation of palmitate and choline into Sat PC was increased about twofold in CCSP-IL-4 mice. Although trace doses of radiolabeled Sat PC were cleared from the air spaces and lungs of CCSP-IL-4 mice more slowly than in wild-type mice, net clearance of Sat PC from the lungs of CCSP-IL-4 mice was sixfold higher in the IL-4 mice than in wild-type mice because of the larger Sat PC pool sizes. Expression of IL-4 in Clara cells increased surfactant lipid synthesis and clearance, establishing a new equilibrium with increased surfactant pools and an alveolar proteinosis associated with a selective increase in SP-D protein, demonstrating a previously unexpected effect of IL-4 in pulmonary surfactant homeostasis.

AB - Mice that express interleukin (IL)-4 in Clara cells (CCSP-IL-4) develop chronic airway inflammation and an alveolar proteinosis-like syndrome. To identify the role of IL-4 in surfactant homeostasis, we measured lipid and protein metabolism in the lungs of CCSP-IL-4 mice in vivo. Alveolar saturated phosphatidylcholine (Sat PC) pools were increased 6.5-fold and lung tissue Sat PC pools were increased 4.8-fold in the IL-4 transgenic mice. Whereas surfactant protein (SP) A was increased proportionately to Sat PC, SP-D was increased approximately 90-fold in the IL-4 mice compared with wild-type mice and was associated with 2.8-fold increase in SP-D mRNA. The incorporation of palmitate and choline into Sat PC was increased about twofold in CCSP-IL-4 mice. Although trace doses of radiolabeled Sat PC were cleared from the air spaces and lungs of CCSP-IL-4 mice more slowly than in wild-type mice, net clearance of Sat PC from the lungs of CCSP-IL-4 mice was sixfold higher in the IL-4 mice than in wild-type mice because of the larger Sat PC pool sizes. Expression of IL-4 in Clara cells increased surfactant lipid synthesis and clearance, establishing a new equilibrium with increased surfactant pools and an alveolar proteinosis associated with a selective increase in SP-D protein, demonstrating a previously unexpected effect of IL-4 in pulmonary surfactant homeostasis.

UR - http://www.scopus.com/inward/record.url?scp=0033983678&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033983678&partnerID=8YFLogxK

M3 - Article

VL - 278

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 1040-0605

IS - 1 22-1

ER -