Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 30676-30685 |
| Number of pages | 10 |
| Journal | The Journal of Biological Chemistry |
| Volume | 285 |
| Issue number | 40 |
| DOIs | |
| Publication status | Published - 2010 |
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Keywords
- Animals
- Candida albicans
- Candidiasis
- Cell Line
- Cyclooxygenase 2
- Eicosanoids
- Enzyme Activation
- Gene Expression Regulation, Enzymologic
- Group IV Phospholipases A2
- Lectins, C-Type
- MAP Kinase Signaling System
- Macrophages, Peritoneal
- Membrane Proteins
- Mice
- Mice, Inbred BALB C
- Mice, Knockout
- Myeloid Differentiation Factor 88
- Nerve Tissue Proteins
- Phosphorylation
Cite this
Pathways regulating cytosolic phospholipase A2 activation and eicosanoid production in macrophages by Candida albicans. / Suram, Saritha; Gangelhoff, Todd A; Taylor, Philip R; Rosas, Marcela; Brown, Gordon D; Bonventre, Joseph V; Akira, Shizuo; Uematsu, Satoshi; Williams, David L; Murphy, Robert C; Leslie, Christina C.
In: The Journal of Biological Chemistry, Vol. 285, No. 40, 2010, p. 30676-30685.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pathways regulating cytosolic phospholipase A2 activation and eicosanoid production in macrophages by Candida albicans
AU - Suram, Saritha
AU - Gangelhoff, Todd A
AU - Taylor, Philip R
AU - Rosas, Marcela
AU - Brown, Gordon D
AU - Bonventre, Joseph V
AU - Akira, Shizuo
AU - Uematsu, Satoshi
AU - Williams, David L
AU - Murphy, Robert C
AU - Leslie, Christina C
PY - 2010
Y1 - 2010
N2 - Resident tissue macrophages are activated by the fungal pathogen Candida albicans to release eicosanoids, which are important modulators of inflammation and immune responses. Our objective was to identify the macrophage receptors engaged by C. albicans that mediate activation of group IVA cytosolic phospholipase A(2) (cPLA(2)a), a regulatory enzyme that releases arachidonic acid (AA) for production of prostaglandins and leukotrienes. A comparison of peritoneal macrophages from wild type and knock-out mice demonstrates that the ß-glucan receptor Dectin-1 and MyD88 regulate early release of AA and eicosanoids in response to C. albicans. However, cyclooxygenase 2 (COX2) expression and later phase eicosanoid production are defective in MyD88(-/-) but not Dectin-1(-/-) macrophages. Furthermore, C. albicans-stimulated activation of MAPK and phosphorylation of cPLA(2)a on Ser-505 are regulated by MyD88 and not Dectin-1. In contrast, Dectin-1 mediates MAPK activation, cPLA(2)a phosphorylation, and COX2 expression in response to particulate ß-glucan suggesting that other receptors engaged by C. albicans preferentially mediate these responses. Results also implicate the mannan-binding receptor Dectin-2 in regulating cPLA(2)a. C. albicans-stimulated MAPK activation and AA release are blocked by d-mannose and Dectin-2-specific antibody, and overexpression of Dectin-2 in RAW264.7 macrophages enhances C. albicans-stimulated MAPK activation, AA release, and COX2 expression. In addition, calcium mobilization is enhanced in RAW264.7 macrophages overexpressing Dectin-1 or -2. The results demonstrate that C. albicans engages both ß-glucan and mannan-binding receptors on macrophages that act with MyD88 to regulate the activation of cPLA(2)a and eicosanoid production.
AB - Resident tissue macrophages are activated by the fungal pathogen Candida albicans to release eicosanoids, which are important modulators of inflammation and immune responses. Our objective was to identify the macrophage receptors engaged by C. albicans that mediate activation of group IVA cytosolic phospholipase A(2) (cPLA(2)a), a regulatory enzyme that releases arachidonic acid (AA) for production of prostaglandins and leukotrienes. A comparison of peritoneal macrophages from wild type and knock-out mice demonstrates that the ß-glucan receptor Dectin-1 and MyD88 regulate early release of AA and eicosanoids in response to C. albicans. However, cyclooxygenase 2 (COX2) expression and later phase eicosanoid production are defective in MyD88(-/-) but not Dectin-1(-/-) macrophages. Furthermore, C. albicans-stimulated activation of MAPK and phosphorylation of cPLA(2)a on Ser-505 are regulated by MyD88 and not Dectin-1. In contrast, Dectin-1 mediates MAPK activation, cPLA(2)a phosphorylation, and COX2 expression in response to particulate ß-glucan suggesting that other receptors engaged by C. albicans preferentially mediate these responses. Results also implicate the mannan-binding receptor Dectin-2 in regulating cPLA(2)a. C. albicans-stimulated MAPK activation and AA release are blocked by d-mannose and Dectin-2-specific antibody, and overexpression of Dectin-2 in RAW264.7 macrophages enhances C. albicans-stimulated MAPK activation, AA release, and COX2 expression. In addition, calcium mobilization is enhanced in RAW264.7 macrophages overexpressing Dectin-1 or -2. The results demonstrate that C. albicans engages both ß-glucan and mannan-binding receptors on macrophages that act with MyD88 to regulate the activation of cPLA(2)a and eicosanoid production.
KW - Animals
KW - Candida albicans
KW - Candidiasis
KW - Cell Line
KW - Cyclooxygenase 2
KW - Eicosanoids
KW - Enzyme Activation
KW - Gene Expression Regulation, Enzymologic
KW - Group IV Phospholipases A2
KW - Lectins, C-Type
KW - MAP Kinase Signaling System
KW - Macrophages, Peritoneal
KW - Membrane Proteins
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Knockout
KW - Myeloid Differentiation Factor 88
KW - Nerve Tissue Proteins
KW - Phosphorylation
U2 - 10.1074/jbc.M110.143800
DO - 10.1074/jbc.M110.143800
M3 - Article
VL - 285
SP - 30676
EP - 30685
JO - The Journal of Biological Chemistry
JF - The Journal of Biological Chemistry
SN - 0021-9258
IS - 40
ER -