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CD14-de pendent mechanism for endotoxin-mediated nitric oxide synthesis in murine macrophages

Publication ,  Journal Article
Schroeder, RA; Delatorre, A; Kuo, PC
Published in: American Journal of Physiology
December 1, 1997

-Endotoxin-mediated macrophage synthesis of nitric oxide (NO) is associated with immune effector function, intercellular communication, leukocyte adhesion, vascular integrity, and neurotransmission. However, little is known of the cellular receptor and signal transduction pathway by which endotoxin induces NO production. With the use of a model of ANA-1 murine macrophages, we stimulated NO production by incubation with increasing concentrations of endotoxin and 5% fetal calf serum. In selected instances, the anti-CD14 antibody, ED9, was added. Endotoxin-mediated NO synthesis was dependent on CD14 function and the presence of an additional serum factor. Endotoxin treatment increased plasma membrane GTPase activity and 35S-labeled guanosine 5′-O-(3-thiotriphosphate) ([35S]GTPγS) binding. Conversely, coincubation of cells with endotoxin and the heterotrimeric G protein inhibitors, suramin and guanosine 5′-O-(2-thiodiphosphate) trilithium salt, was associated with decreased NO synthesis, plasma membrane GTPase activity, and [35S]GTPγS binding. Blockade of CD14 or G protein function was associated with ablation of endotoxin-mediated inducible NO synthase (iNOS) protein expression, iNOS mRNA levels, and iNOS gene transcription, as determined by immunoblot, reverse transcriptase-polymerase chain reaction, and nuclear run-on analyses, respectively. These results indicate that endotoxin-mediated NO synthesis is a CD14-heterotrimeric G protein-dependent process. Copyright ©1997 the American Physiological Society.

Duke Scholars

Published In

American Journal of Physiology

ISSN

0002-9513

Publication Date

December 1, 1997

Volume

273

Issue

3 PART 1

Related Subject Headings

  • Cardiovascular System & Hematology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Schroeder, R. A., Delatorre, A., & Kuo, P. C. (1997). CD14-de pendent mechanism for endotoxin-mediated nitric oxide synthesis in murine macrophages. American Journal of Physiology, 273(3 PART 1).
Schroeder, R. A., A. Delatorre, and P. C. Kuo. “CD14-de pendent mechanism for endotoxin-mediated nitric oxide synthesis in murine macrophages.” American Journal of Physiology 273, no. 3 PART 1 (December 1, 1997).
Schroeder RA, Delatorre A, Kuo PC. CD14-de pendent mechanism for endotoxin-mediated nitric oxide synthesis in murine macrophages. American Journal of Physiology. 1997 Dec 1;273(3 PART 1).
Schroeder, R. A., et al. “CD14-de pendent mechanism for endotoxin-mediated nitric oxide synthesis in murine macrophages.” American Journal of Physiology, vol. 273, no. 3 PART 1, Dec. 1997.
Schroeder RA, Delatorre A, Kuo PC. CD14-de pendent mechanism for endotoxin-mediated nitric oxide synthesis in murine macrophages. American Journal of Physiology. 1997 Dec 1;273(3 PART 1).

Published In

American Journal of Physiology

ISSN

0002-9513

Publication Date

December 1, 1997

Volume

273

Issue

3 PART 1

Related Subject Headings

  • Cardiovascular System & Hematology