Effects of decreased calmodulin protein on the survival mechanisms of alveolar macrophages during Pneumocystis pneumonia

Mark E. Lasbury, Pamela J. Durant, Chung Ping Liao, Chao-Hung Lee

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Pneumocystis infection causes increased intracellular levels of reactive oxygen species (ROS) and the subsequent apoptosis of alveolar macrophages (Amø). Assessments of key prosurvival molecules in Amø and bronchoalveolar lavage fluids from infected rats and mice showed low levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and reduced activation of phosphoinositide-3 kinase (PI-3K). Ubiquitous calcium-sensing protein calmodulin protein and mRNA levels were also reduced in Amø during Pneumocystis pneumonia (Pcp). Calmodulin has been implicated in control of GM-CSF production and PI-3K activation in other immune cell types. Experiments to determine the control of GM-CSF and PI-3K by calmodulin in Amø showed that GM-CSF expression and PI-3K activation could not be induced when calmodulin was inhibited. Calmodulin inhibition also led to increased levels of ROS and apoptosis in cells exposed to bronchoalveolar lavage fluids from infected animals. Supplementation of Amø with exogenous calmodulin increased survival signaling via GM-CSF and PI-3K and reduced ROS and apoptosis. These data support the hypotheses that calmodulin levels at least partially control survival signaling in Amø and that restoration of GM-CSF or PI-3K signaling will improve host response to the organism.

Original languageEnglish
Pages (from-to)3344-3354
Number of pages11
JournalInfection and Immunity
Volume77
Issue number8
DOIs
StatePublished - Aug 2009

Fingerprint

Pneumocystis Pneumonia
Alveolar Macrophages
Calmodulin
1-Phosphatidylinositol 4-Kinase
Granulocyte-Macrophage Colony-Stimulating Factor
Bronchoalveolar Lavage Fluid
Proteins
Reactive Oxygen Species
Apoptosis
Pneumocystis Infections
Calcium
Messenger RNA

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Effects of decreased calmodulin protein on the survival mechanisms of alveolar macrophages during Pneumocystis pneumonia. / Lasbury, Mark E.; Durant, Pamela J.; Liao, Chung Ping; Lee, Chao-Hung.

In: Infection and Immunity, Vol. 77, No. 8, 08.2009, p. 3344-3354.

Research output: Contribution to journalArticle

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