LIGAND-BINDING TO THE (1-]3)-BETA-D-GLUCAN RECEPTOR STIMULATES NF-KAPPA-B ACTIVATION, BUT NOT APOPTOSIS IN U937 CELLS

Recent data suggest that sepsis stimulates macrophage apoptosis (A(o)) with subsequent induction of macrophage dysfunction. Nuclear factor-k appaB (NF kappa B) activation has been linked to A(o) in either a pro- or antiapoptotic role. Glucans are biological response modifiers whic h exert antisepsis activity. This investigation examined the effect of (1-3)-beta-D-glucan receptor binding by a high affinity ligand on A(o ) and NF kappa B activation in U937 cells in the presence or absence o f LPS. A high affinity glucan ligand (IC50 = 23 nM) activated NF kappa B, but did not induce A(o) or significantly alter LPS induced U937 A, . These data indicate that: i) modulation of the macrophage (1-3)-beta -D-glucan receptor stimulates NF kappa B; ii) does not induce A(o) or significantly diminish LPS induced A(o) and iii) activation of the U93 7 FAS receptor does not alter the relative A(o) responses in glucan an d LPS treated cells. (C) 1998 Academic Press.