Activation of rat macrophages by Betafectin PGG-glucan requires cross-linking of membrane receptors distinct from complement receptor three (CR3)

Michalek, M T; Melican, D.; Brunke-Reese, Deborah; Langevin, Matthew; Lemerise, Kristen; Galbraith, W.; Patchen, Myra L.; Mackin, William M.

doi:10.1002/jlb.64.3.337

Cited by 45 publications

(24 citation statements)

References 56 publications

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“…Additional studies suggest that glucan polymers may cross-link spatially separated membrane receptors to induce immunomodulatory effects. Thus, the length and structural complexity of any species ␤-glucan likely modulate both the type and the strength of the elicited host responses (57,58).…”

Section: Discussionmentioning

confidence: 99%

Pneumocystis carinii Cell Wall β-Glucans Initiate Macrophage Inflammatory Responses through NF-κB Activation

Lebron¹,

Vassallo²,

Puri³

et al. 2003

Journal of Biological Chemistry

110

101

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␤-Glucans are major structural components of fungi. We have recently reported that the pathogenic fungus Pneumocystis carinii assembles a ␤-glucan-rich cell wall that potently activates alveolar macrophages to release pro-inflammatory cytokines and chemokines. Purified P. carinii ␤-glucans predictably induce both cytokine generation and associated neutrophilic lung inflammation. Herein, we demonstrate that P. carinii ␤-glucaninduced macrophage stimulation results from activation of NF-B. Although analogous to macrophage activation induced by bacterial lipopolysaccharide (LPS), P. carinii ␤-glucan-induced macrophage NF-B activation exhibits distinctly different kinetics, with slower induction and longer duration compared with LPS stimulation. Macrophage activation in response to P. carinii ␤-glucan was also substantially inhibited with the NF-B antagonist pyrrolidine dithiocarbamate. In addition to different kinetics of NF-B activation, P. carinii ␤-glucan and LPS also utilize different receptor systems to induce macrophage activation. Macrophages from Toll-like receptor 4-deficient and wild type mice produced equivalent amounts of tumor necrosis factor ␣ when stimulated with P. carinii ␤-glucan. However, Toll-like receptor 4-deficient macrophages were refractory to stimulation with LPS. In contrast, MyD88-deficient macrophages exhibited a significant (though partial) blunted response to P. carinii ␤-glucan. These data demonstrate that P. carinii ␤-glucan acts as potent inducer of macrophage activation through NF-B utilizing cellular receptors and signaling pathways distinct from LPS.

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Section: Discussionmentioning

confidence: 99%

Pneumocystis carinii Cell Wall β-Glucans Initiate Macrophage Inflammatory Responses through NF-κB Activation

Lebron¹,

Vassallo²,

Puri³

et al. 2003

Journal of Biological Chemistry

110

101

View full text Add to dashboard Cite

show abstract

“…Investigations with other purified fungal ␤-glucans have demonstrated that particulate and/or poorly soluble ␤-1,3 glucans directly induce mononuclear cells to release TNF-␣ and IL-1␤ in vitro (10,54). It has been postulated that particulate (but not soluble) ␤-glucans elicit these responses because of cross-linking or immobilization of ␤-glucan receptors (55).…”

Section: Discussionmentioning

confidence: 99%

Isolated Pneumocystis carinii Cell Wall Glucan Provokes Lower Respiratory Tract Inflammatory Responses

Vassallo¹,

Standing²,

Limper

2000

The Journal of Immunology

142

153

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Macrophage-induced lung inflammation contributes substantially to respiratory failure during Pneumocystis carinii pneumonia. We isolated a P. carinii cell wall fraction rich in glucan carbohydrate, which potently induces TNF-α and macrophage-inflammatory protein-2 generation from alveolar macrophages. Instillation of this purified P. carinii carbohydrate cell wall fraction into healthy rodents is accompanied by substantial increases in whole lung TNF-α generation and is associated with neutrophilic infiltration of the lungs. Digestion of the P. carinii cell wall isolate with zymolyase, a preparation containing predominantly β-1,3 glucanase, substantially reduces the ability of this P. carinii cell wall fraction to activate alveolar macrophages, thus suggesting that β-glucan components of the P. carinii cell wall largely mediate TNF-α release. Furthermore, the soluble carbohydrate β-glucan receptor antagonists laminariheptaose and laminarin also substantially reduce the ability of the P. carinii cell wall isolate to stimulate macrophage-inflammatory activation. In contrast, soluble α-mannan, a preparation that antagonizes macrophage mannose receptors, had minimal effect on TNF-α release induced by the P. carinii cell wall fraction. P. carinii β-glucan-induced TNF-α release from alveolar macrophages was also inhibited by both dexamethasone and pentoxifylline, two pharmacological agents with potential activity in controlling P. carinii-induced lung inflammation. These data demonstrate that P. carinii β-glucan cell wall components can directly stimulate alveolar macrophages to release proinflammatory cytokines mainly through interaction with cognate β-glucan receptors on the phagocyte.

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“…Photoactivation of the plate surface allows formation of a covalent linkage with the passively adsorbed carbohydrates. The method has been shown to have an approximate binding efficiency of 10 -20% (18). The final content of ␤-glucan on the assay plate is similarly reduced.…”

Section: Preparation Of Microtiter Plates: Immobilization Of Polysaccmentioning

confidence: 99%

Integrin Engagement Mediates the Human Polymorphonuclear Leukocyte Response to a Fungal Pathogen-Associated Molecular Pattern

Lavigne

O’Brien

Kim

et al. 2007

The Journal of Immunology

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Extravasation of leukocytes from peripheral blood is required for an effective inflammatory response at sites of tissue infection. Integrins help mediate extravasation and navigate the leukocyte to the infectious source. A novel role for integrins in regulating the effector response to a cell wall component of fungal pathogens is the subject of the current study. Although phagocytosis is useful for clearance of unicellular fungi, the immune response against large, noningestible hyphae is not well-understood. Fungal β-glucan, a pathogen-associated molecular pattern, activates production of superoxide anion in leukocytes without the need for phagocytosis. To model polymorphonuclear leukocyte (PMN) recognition of fungi under conditions in which phagocytosis cannot occur, β-glucan was covalently immobilized onto tissue culture plastic. Plasma membrane-associated respiratory burst was measured by reduction of ferricytochrome C. Results show that the human PMN oxidative burst response to immobilized β-glucan is suppressed by addition of β1 integrin ligands to the β-glucan matrix. Suppression was dose dependent and steric hindrance was ruled out. β1 integrin ligands did not affect respiratory burst to ingestible β-glucan-containing particles, phorbol esters or live yeast hyphae. Furthermore, in the absence of matrix, Ab activation of VLA3 or VLA5, but not other β1 integrins, also prevented β-glucan-induced respiratory burst. β1-induced suppression was blocked and burst response restored by treating neutrophils with either the cell-binding fragment of soluble human Fn, cyclic RGD peptide, or Ab specific to VLA3 or VLA5. Together these findings extend the functional role of β1 integrins to include modulating PMN respiratory burst to a pathogen-associated molecular pattern.

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Activation of rat macrophages by Betafectin PGG-glucan requires cross-linking of membrane receptors distinct from complement receptor three (CR3)

Cited by 45 publications

References 56 publications

Pneumocystis carinii Cell Wall β-Glucans Initiate Macrophage Inflammatory Responses through NF-κB Activation

Pneumocystis carinii Cell Wall β-Glucans Initiate Macrophage Inflammatory Responses through NF-κB Activation

Isolated Pneumocystis carinii Cell Wall Glucan Provokes Lower Respiratory Tract Inflammatory Responses

Integrin Engagement Mediates the Human Polymorphonuclear Leukocyte Response to a Fungal Pathogen-Associated Molecular Pattern

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