Defective nitric oxide production by alveolar macrophages during Pneumocystis pneumonia

Mark E. Lasbury, Chung Ping Liao, Chadi Hage, Pamela J. Durant, Dennis Tschang, Shao Hung Wang, Chen Zhang, Chao-Hung Lee

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The effect of nitric oxide (NO) on Pneumocystis (Pc) organisms, the role of NO in the defense against infection with Pc, and the production of NO by alveolar macrophages (AMs) during Pneumocystis pneumonia (PCP) were investigated. The results indicate that NO was toxic to Pc organisms and inhibited their proliferation in culture. When the production of NO was inhibited by intraperitoneal injection of rats with the nitric oxide synthase inhibitor L-N5-(1-iminoethyl) ornithine, progression of Pc infection in immunocompetent rats was enhanced. Concentrations of NO in bronchoalveolar lavage fluids from immunosuppressed, Pc-infected rats and mice were greatly reduced, compared with those from uninfected animals, and AMs from these animals were defective in NO production. However, inducible nitric oxide synthase (iNOS) mRNA and protein concentrations were high in AMs from Pc-infected rats and mice. Immunoblot analysis showed that iNOS in AMs from Pc-infected rats existed primarily as a monomer, but the homo-dimerization of iNOS monomers was required for the production of NO. When iNOS dimerization cofactors, including calmodulin, were added to macrophage lysates, iNOS dimerization increased, whereas incubation of the same lysates with all cofactors except calmodulin did not rescue iNOS dimer formation. These data suggest that NO is important in the defense against Pc infection, but that the production of NO in AMs during PCP is defective because of the reduced dimerization of iNOS.

Original languageEnglish
Pages (from-to)540-547
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume44
Issue number4
DOIs
StatePublished - Apr 1 2011

Fingerprint

Pneumocystis Pneumonia
Alveolar Macrophages
Nitric Oxide
Nitric Oxide Synthase Type II
Pneumocystis
Dimerization
Pneumocystis Infections
Rats
Calmodulin
Animals
Monomers
Macrophages
Poisons
Bronchoalveolar Lavage Fluid
Intraperitoneal Injections
Nitric Oxide Synthase
Dimers
Messenger RNA

Keywords

  • Alveolar macrophage
  • Calmodulin
  • iNOS
  • Nitric oxide
  • Pneumocystis

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Defective nitric oxide production by alveolar macrophages during Pneumocystis pneumonia. / Lasbury, Mark E.; Liao, Chung Ping; Hage, Chadi; Durant, Pamela J.; Tschang, Dennis; Wang, Shao Hung; Zhang, Chen; Lee, Chao-Hung.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 44, No. 4, 01.04.2011, p. 540-547.

Research output: Contribution to journalArticle

Lasbury, Mark E. ; Liao, Chung Ping ; Hage, Chadi ; Durant, Pamela J. ; Tschang, Dennis ; Wang, Shao Hung ; Zhang, Chen ; Lee, Chao-Hung. / Defective nitric oxide production by alveolar macrophages during Pneumocystis pneumonia. In: American Journal of Respiratory Cell and Molecular Biology. 2011 ; Vol. 44, No. 4. pp. 540-547.
@article{9688288df28040d88c6a5f1faa0a1771,
title = "Defective nitric oxide production by alveolar macrophages during Pneumocystis pneumonia",
abstract = "The effect of nitric oxide (NO) on Pneumocystis (Pc) organisms, the role of NO in the defense against infection with Pc, and the production of NO by alveolar macrophages (AMs) during Pneumocystis pneumonia (PCP) were investigated. The results indicate that NO was toxic to Pc organisms and inhibited their proliferation in culture. When the production of NO was inhibited by intraperitoneal injection of rats with the nitric oxide synthase inhibitor L-N5-(1-iminoethyl) ornithine, progression of Pc infection in immunocompetent rats was enhanced. Concentrations of NO in bronchoalveolar lavage fluids from immunosuppressed, Pc-infected rats and mice were greatly reduced, compared with those from uninfected animals, and AMs from these animals were defective in NO production. However, inducible nitric oxide synthase (iNOS) mRNA and protein concentrations were high in AMs from Pc-infected rats and mice. Immunoblot analysis showed that iNOS in AMs from Pc-infected rats existed primarily as a monomer, but the homo-dimerization of iNOS monomers was required for the production of NO. When iNOS dimerization cofactors, including calmodulin, were added to macrophage lysates, iNOS dimerization increased, whereas incubation of the same lysates with all cofactors except calmodulin did not rescue iNOS dimer formation. These data suggest that NO is important in the defense against Pc infection, but that the production of NO in AMs during PCP is defective because of the reduced dimerization of iNOS.",
keywords = "Alveolar macrophage, Calmodulin, iNOS, Nitric oxide, Pneumocystis",
author = "Lasbury, {Mark E.} and Liao, {Chung Ping} and Chadi Hage and Durant, {Pamela J.} and Dennis Tschang and Wang, {Shao Hung} and Chen Zhang and Chao-Hung Lee",
year = "2011",
month = "4",
day = "1",
doi = "10.1165/rcmb.2009-0367OC",
language = "English",
volume = "44",
pages = "540--547",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "4",

}

TY - JOUR

T1 - Defective nitric oxide production by alveolar macrophages during Pneumocystis pneumonia

AU - Lasbury, Mark E.

AU - Liao, Chung Ping

AU - Hage, Chadi

AU - Durant, Pamela J.

AU - Tschang, Dennis

AU - Wang, Shao Hung

AU - Zhang, Chen

AU - Lee, Chao-Hung

PY - 2011/4/1

Y1 - 2011/4/1

N2 - The effect of nitric oxide (NO) on Pneumocystis (Pc) organisms, the role of NO in the defense against infection with Pc, and the production of NO by alveolar macrophages (AMs) during Pneumocystis pneumonia (PCP) were investigated. The results indicate that NO was toxic to Pc organisms and inhibited their proliferation in culture. When the production of NO was inhibited by intraperitoneal injection of rats with the nitric oxide synthase inhibitor L-N5-(1-iminoethyl) ornithine, progression of Pc infection in immunocompetent rats was enhanced. Concentrations of NO in bronchoalveolar lavage fluids from immunosuppressed, Pc-infected rats and mice were greatly reduced, compared with those from uninfected animals, and AMs from these animals were defective in NO production. However, inducible nitric oxide synthase (iNOS) mRNA and protein concentrations were high in AMs from Pc-infected rats and mice. Immunoblot analysis showed that iNOS in AMs from Pc-infected rats existed primarily as a monomer, but the homo-dimerization of iNOS monomers was required for the production of NO. When iNOS dimerization cofactors, including calmodulin, were added to macrophage lysates, iNOS dimerization increased, whereas incubation of the same lysates with all cofactors except calmodulin did not rescue iNOS dimer formation. These data suggest that NO is important in the defense against Pc infection, but that the production of NO in AMs during PCP is defective because of the reduced dimerization of iNOS.

AB - The effect of nitric oxide (NO) on Pneumocystis (Pc) organisms, the role of NO in the defense against infection with Pc, and the production of NO by alveolar macrophages (AMs) during Pneumocystis pneumonia (PCP) were investigated. The results indicate that NO was toxic to Pc organisms and inhibited their proliferation in culture. When the production of NO was inhibited by intraperitoneal injection of rats with the nitric oxide synthase inhibitor L-N5-(1-iminoethyl) ornithine, progression of Pc infection in immunocompetent rats was enhanced. Concentrations of NO in bronchoalveolar lavage fluids from immunosuppressed, Pc-infected rats and mice were greatly reduced, compared with those from uninfected animals, and AMs from these animals were defective in NO production. However, inducible nitric oxide synthase (iNOS) mRNA and protein concentrations were high in AMs from Pc-infected rats and mice. Immunoblot analysis showed that iNOS in AMs from Pc-infected rats existed primarily as a monomer, but the homo-dimerization of iNOS monomers was required for the production of NO. When iNOS dimerization cofactors, including calmodulin, were added to macrophage lysates, iNOS dimerization increased, whereas incubation of the same lysates with all cofactors except calmodulin did not rescue iNOS dimer formation. These data suggest that NO is important in the defense against Pc infection, but that the production of NO in AMs during PCP is defective because of the reduced dimerization of iNOS.

KW - Alveolar macrophage

KW - Calmodulin

KW - iNOS

KW - Nitric oxide

KW - Pneumocystis

UR - http://www.scopus.com/inward/record.url?scp=79953748201&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953748201&partnerID=8YFLogxK

U2 - 10.1165/rcmb.2009-0367OC

DO - 10.1165/rcmb.2009-0367OC

M3 - Article

VL - 44

SP - 540

EP - 547

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 4

ER -