Cytosolic phospholipase A2 activation by Candida albicans in alveolar macrophages

Rajinder P Parti, Robyn Loper, Gordon D Brown, Siamon Gordon, Philip R Taylor, Joseph V Bonventre, Robert C Murphy, David L Williams, Christina C Leslie

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Candida albicans is an increasingly important pulmonary fungal pathogen. Resident alveolar macrophages are important in host defense against opportunistic fungal infections. Activation of Group IVA cytosolic phospholipase A(2)alpha (cPLA(2)alpha) in macrophages initiates arachidonic acid (AA) release for production of eicosanoids, which regulate inflammation and immune responses. We investigated the ability of C. albicans to activate cPLA(2)alpha in unprimed alveolar macrophages and after priming with granulocyte macrophage colony-stimulating factor (GM-CSF), which regulates alveolar macrophage maturation. AA was released within minutes by GM-CSF-primed but not unprimed alveolar macrophages in response to C. albicans, and was blocked by soluble glucan phosphate (S-GP). The expression of the beta-glucan receptor dectin-1 was increased in GM-CSF-primed macrophages, and AA release from GM-CSF-primed dectin-1(-/-) alveolar macrophages was reduced to basal levels. The enhanced activation of extracellular signal-regulated kinases and phosphorylation of cPLA(2)alpha on Ser-505 that occurred in GM-CSF-primed macrophages were reduced by MEK1 and Syk inhibitors, which also suppressed AA release. At later times after C. albicans infection (6 h), unprimed and GM-CSF-primed macrophages released similar levels of AA. The expression of cyclooxygenase 2 and prostanoid production at 6 hours was higher in GM-CSF-primed macrophages, but the responses were not dependent on dectin-1. However, dectin-1 contributed to the C. albicans-stimulated increase in TNF-alpha production that occurred in GM-CSF-primed macrophages. The results demonstrate that dectin-1 mediates the acute activation of cPLA(2)alpha in GM-CSF-primed alveolar macrophages, but not in the more delayed phase of AA release and GM-CSF-dependent prostanoid production.
Original languageEnglish
Pages (from-to)415-23
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume42
Issue number4
Early online date5 Jun 2009
DOIs
Publication statusPublished - Apr 2010

Fingerprint

Cytosolic Phospholipases A2
Candida
Alveolar Macrophages
Granulocyte-Macrophage Colony-Stimulating Factor
Candida albicans
Chemical activation
Macrophages
Group IV Phospholipases A2
Arachidonic Acid
Prostaglandins
Phosphorylation
Eicosanoids
Mycoses
Extracellular Signal-Regulated MAP Kinases
Opportunistic Infections
Pathogens
Cyclooxygenase 2
Tumor Necrosis Factor-alpha
dectin 1

Keywords

  • animals
  • arachidonic acid
  • Candida albicans
  • candidiasis
  • enzyme activation
  • granulocyte-macrophage colony-stimulating factor
  • group IV phospholipases A2
  • intracellular signaling peptides and proteins
  • MAP kinase kinase 1
  • MAP kinase signaling system
  • macrophages, alveolar
  • membrane proteins
  • mice
  • mice, inbred BALB C
  • mice, inbred ICR
  • mice, knockout
  • nerve tissue proteins
  • phosphorylation
  • protein kinase inhibitors
  • protein-tyrosine kinases
  • time factors
  • tumor necrosis factor-alpha
  • cytosolic phospholipase A2
  • dectin-1
  • alveolar macrophages
  • granulocyte macrophage colony-stimulating factor

Cite this

Parti, R. P., Loper, R., Brown, G. D., Gordon, S., Taylor, P. R., Bonventre, J. V., ... Leslie, C. C. (2010). Cytosolic phospholipase A2 activation by Candida albicans in alveolar macrophages. American Journal of Respiratory Cell and Molecular Biology, 42(4), 415-23. https://doi.org/10.1165/rcmb.2009-0110OC

Cytosolic phospholipase A2 activation by Candida albicans in alveolar macrophages. / Parti, Rajinder P; Loper, Robyn; Brown, Gordon D; Gordon, Siamon; Taylor, Philip R; Bonventre, Joseph V; Murphy, Robert C; Williams, David L; Leslie, Christina C.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 42, No. 4, 04.2010, p. 415-23.

Research output: Contribution to journalArticle

Parti, RP, Loper, R, Brown, GD, Gordon, S, Taylor, PR, Bonventre, JV, Murphy, RC, Williams, DL & Leslie, CC 2010, 'Cytosolic phospholipase A2 activation by Candida albicans in alveolar macrophages', American Journal of Respiratory Cell and Molecular Biology, vol. 42, no. 4, pp. 415-23. https://doi.org/10.1165/rcmb.2009-0110OC
Parti, Rajinder P ; Loper, Robyn ; Brown, Gordon D ; Gordon, Siamon ; Taylor, Philip R ; Bonventre, Joseph V ; Murphy, Robert C ; Williams, David L ; Leslie, Christina C. / Cytosolic phospholipase A2 activation by Candida albicans in alveolar macrophages. In: American Journal of Respiratory Cell and Molecular Biology. 2010 ; Vol. 42, No. 4. pp. 415-23.
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AB - Candida albicans is an increasingly important pulmonary fungal pathogen. Resident alveolar macrophages are important in host defense against opportunistic fungal infections. Activation of Group IVA cytosolic phospholipase A(2)alpha (cPLA(2)alpha) in macrophages initiates arachidonic acid (AA) release for production of eicosanoids, which regulate inflammation and immune responses. We investigated the ability of C. albicans to activate cPLA(2)alpha in unprimed alveolar macrophages and after priming with granulocyte macrophage colony-stimulating factor (GM-CSF), which regulates alveolar macrophage maturation. AA was released within minutes by GM-CSF-primed but not unprimed alveolar macrophages in response to C. albicans, and was blocked by soluble glucan phosphate (S-GP). The expression of the beta-glucan receptor dectin-1 was increased in GM-CSF-primed macrophages, and AA release from GM-CSF-primed dectin-1(-/-) alveolar macrophages was reduced to basal levels. The enhanced activation of extracellular signal-regulated kinases and phosphorylation of cPLA(2)alpha on Ser-505 that occurred in GM-CSF-primed macrophages were reduced by MEK1 and Syk inhibitors, which also suppressed AA release. At later times after C. albicans infection (6 h), unprimed and GM-CSF-primed macrophages released similar levels of AA. The expression of cyclooxygenase 2 and prostanoid production at 6 hours was higher in GM-CSF-primed macrophages, but the responses were not dependent on dectin-1. However, dectin-1 contributed to the C. albicans-stimulated increase in TNF-alpha production that occurred in GM-CSF-primed macrophages. The results demonstrate that dectin-1 mediates the acute activation of cPLA(2)alpha in GM-CSF-primed alveolar macrophages, but not in the more delayed phase of AA release and GM-CSF-dependent prostanoid production.

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