Both mannose and β-glucan receptors are involved in phagocytosis of unopsonized, heat-killed <i>Saccharomyces cerevisiae</i> by murine macrophages

Diebold

Journal of Biological Chemistry

et al. 2004

Phagocytosis is accompanied by the production of superoxide by the NADPH oxidase complex, for which GTP-bound Rac is essential. We wanted to determine whether Rho is also involved in the production of superoxide during phagocytosis. Inhibition of Rho by Tat-C3 exoenzyme (Tat-C3) blocked superoxide formation and curtailed the phagocytosis of serum-(SOZ), C3bi-(COZ), and IgG-opsonized zymosan (IOZ) particles. Tat-C3 did not affect superoxide formation in response to phorbol myristate acetate (PMA), formyl Met-Leu-Phe (fMLP), or macrophage colony-stimulating factor (M-CSF). Superoxide formation was also reduced in J774 cells transfected with a cDNA expressing dominant-negative form of RhoA (N19RhoA). However, purified prenylated recombinant RhoA did not activate NADPH oxidase in vitro, suggesting that Rho does not interact directly with NADPH oxidase. Tat-C3 inhibited the activity of RhoA, but did not affect that of Rac in vitro or in vivo. It also inhibited the phosphorylation of p47 PHOX , one of the cytosolic components of NADPH oxidase. Taken together, these results suggest that Rho plays an important role in superoxide formation during phagocytosis of SOZ, COZ, and IOZ via phosphorylation of p47 PHOX

“…NOZ particles, which are recognized by mannose receptors, ␣-glucan receptors (55), and CR3 (56), also induced both phagocytosis and superoxide formation (Fig. 7).…”

Section: Rho Gtpasesmentioning

confidence: 98%

Rho Is Involved in Superoxide Formation during Phagocytosis of Opsonized Zymosans

Diebold

Journal of Biological Chemistry

et al. 2004

“…Cellular recognition of nonopsonized zymosan is mediated by mannose and β-glucan receptors (Giaimis et al, 1993). Nonopsonized zymosan can be also ingested through CR3 (Le Cabec et al, 2000), the lectin domain of which binds to soluble β-glucan and mediates phagocytosis of particles containing β-glucan, such as zymosan (Ross et al, 1985).…”

Section: Annose Receptor-m Ediated Phagocytosismentioning

confidence: 99%

Phagocytosis induces superoxide formation and apoptosis in macrophages

Park

2003

Exp Mol Med

homology 2 domain-containing inositol 5'-phosphatase; RhoGDI, Rho GDP dissociation inhibitor; ROK, Rho-dependent protein kinase; ROS, reactive oxygen species, TNFR, tumor necrosis factor receptor; SAPK, stress activating protein kinase; SH2, Src homology 2; SNARE, soluble NSF attachment protein receptor; TNF-α, tumor necorsis factor-α; VAMP, Vesicle-associated membrane protein; WASP, Wiskott-Aldrich syndrome protein A bstractPhagocytosis by inflam m atory cells is an essential step and a part of innate im m unity for protection against foreign pathogens, m icroorganism or dead cells. Phagocytosis, endocytotic events sequel to binding particle ligands to the specific receptors on phagocyte cell surface such as Fcγ recptor (FcγR ), com plem ent receptor (CR ), β-glucan receptor, and phosphatidylserine (PS) receptor, require actin assem bly, pseudopod extension and phagosom e closure. Rho GTPases (R hoA, C dc42, and R ac1) are critically involved in these processes. A brupt superoxide form ation, called as oxidative burst, occurs through NADPH oxidase complex in leukocytes following phagocytosis. NADPH oxidase com plex is com posed of m em brane proteins, p22 PHOX and gp91 PHOX , and cytosolic proteins, p40 PHOX , p47 PHOX and p67 PHOX . The cytosolic subunits and Rac-GTP are translocated to the m embrane, form ing com plete NADPH oxidase com plex with m em brane part subunits. B inding of im unoglobulin G (IgG)-and com plem ent-opsonized particles to FcγR and C R of leukocytes induces apoptosis of the cells, which m ay be due to oxidative burst and accom panying cytochrom e c release and casapase-3 activation.

“…A large number of receptors have been implicated in the recognition of zymosan by murine DC and macrophages, including SIGNR1 [10], mannose receptor [11][12][13][14][15], complement receptor 3 [13][14][15][16][17], dectin-1 [18] ad TLR2/6 [19]. The role of some of these has previously been studied in the context of an atypical cytokine response from zymosan-stimulated DC, characterised by high levels of IL-2 and IL-10, and relatively low levels of IL-12 p70 [20,21].…”

Section: Introductionmentioning

confidence: 99%

Syk‐dependent ERK activation regulates IL‐2 and IL‐10 production by DC stimulated with zymosan

et al. 2007

Zymosan is a particulate yeast preparation that elicits high levels of IL-2 and IL-10 from dendritic cells (DC) and engages multiple innate receptors, including the Syk-coupled receptor dectin-1 and the MyD88-coupled receptor TLR2. Here, we show that induction of IL-2 and IL-10 by zymosan requires activation of ERK MAP kinase in murine DC. Surprisingly, ERK activation in response to zymosan is completely blocked in Sykdeficient DC and unaffected by MyD88 deficiency. Conversely, ERK activation in response to the TLR2 agonist Pam3Cys is completely MyD88 dependent and unaffected by Syk deficiency. The inability of TLR2 ligands in zymosan to couple to ERK may explain the Syk dependence of the IL-2 and IL-10 response in DC and emphasises the importance of Syk-coupled pattern recognition receptors such as dectin-1 in the detection of yeasts. Furthermore, the lack of receptor compensation observed here suggests that responses induced by complex innate stimuli cannot always be predicted by the signalling pathways downstream of individual receptors.