Ligand binding to the (1 --> 3)-beta-D-glucan receptor stimulates NFkappaB activation, but not apoptosis in U937 cells.
Recent data suggest that sepsis stimulates macrophage apoptosis (Ao) with subsequent induction of macrophage dysfunction. Nuclear factor-kappaB (NFkappaB) activation has been linked to Ao in either a pro- or antiapoptotic role. Glucans are biological response modifiers which exert antisepsis activity. This investigation examined the effect of (1-3)-beta-D-glucan receptor binding by a high affinity ligand on Ao and NFkappaB activation in U937 cells in the presence or absence of LPS. A high affinity glucan ligand (IC50 = 23 nM) activated NFkappaB, but did not induce Ao or significantly alter LPS induced U937 Ao. These data indicate that: i) modulation of the macrophage (1-3)-beta-D-glucan receptor stimulates NFkappaB; ii) does not induce Ao or significantly diminish LPS induced Ao and iii) activation of the U937 FAS receptor does not alter the relative Ao responses in glucan and LPS treated cells.
James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, 37614-0575, USA.
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Battle
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D000906:Antibodies / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis; D002460:Cell Line; D004926:Escherichia coli; D053222:Fas Ligand Protein; D005936:Glucans / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D047071:beta-Glucans
D000906:Antibodies; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D005936:Glucans; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011971:Receptors, Immunologic; D047071:beta-Glucans; C045268:beta-glucan receptor; C045938:scleroglucan; C033363:beta-1,3-glucan