Differential regulation of oxidative burst by distinct β-glucan-binding receptors and signaling pathways in human peripheral blood mononuclear cells.
β-Glucans possess broad immunomodulatory properties, including activation of innate immune functions such as oxidative burst activity. The differential roles of complement receptor type 3 (CR3) and Dectin-1, the known β-glucan receptors, and their associated signaling pathways in the generation of oxidative burst induced by different physical forms of Saccharomyces cerevisiae-derived β-glucan were examined in human peripheral blood mononuclear cells (PBMC). In this study whole glucan particle (WGP) or immobilized soluble β-glucan (ISG) was used to represent the phagocytizable or the nonphagocytizable form of a fungus, respectively. Oxidative burst as measured by the formation of superoxide (SO) was detected in PBMC in response to WGP and ISG. SO induction with WGP was concluded to be Dectin-1-mediated and required Src family kinases, phosphatidylinositol-3 kinase and protein kinase B/Akt. In contrast, the SO induction generated by ISG was CR3-mediated and required focal adhesion kinase, spleen tyrosine kinase, phosphatidylinositol-3 kinase, Akt, p38 mitogen activated protein kinase, phospholipase C and protein kinase C. The study results support the hypothesis that human PBMC, specifically monocytes, utilize distinct receptors and overlapping, but distinct, signaling pathways for the oxidative burst in response to challenge by different physical forms of β-glucan.
Biothera, 3388 Mike Collins Drive, Eagan, MN 55121, USA.
Nandita
N
Bose
Lindsay R
LR
Wurst
Anissa S H
AS
Chan
Christine M
CM
Dudney
Megan L
ML
LeRoux
Michael E
ME
Danielson
Paul M
PM
Will
Sonja E
SE
Nodland
Myra L
ML
Patchen
Jurandir J
JJ
Dalle Lucca
Frank J
FJ
Lebeda
John P
JP
Vasilakos
D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D011951:Receptors, Complement / Q000378:metabolism*; D016897:Respiratory Burst; D015398:Signal Transduction; D000099181:Dectin-1
D037181:Lectins, C-Type; D011951:Receptors, Complement; C546929:CLEC7A protein, human; D000099181:Dectin-1
CR3; Dectin-1; human monocytes; oxidative burst; β-glucan