Differential effects of a monoclonal antibody recognizing 3-deoxy-D-manno-2-octulosonic acid on endotoxin-induced activation of pre-B cells and macrophages.

A monoclonal antibody (E1), which reacts with the 3-deoxy-D-manno-2-octulosonic acid region of lipopolysaccharides belonging to the rough Re chemotype (LPS-Re) was used to analyze in vivo and in vitro effects of endotoxin. E1 inhibited LPS-Re-induced activation of Z0Z/3 pre-B cells (expression of surface immunoglobulins) and mature splenic B cells (DNA synthesis) and blocked the binding of biotin-labeled LPS-Re to mouse peritoneal macrophages. However, other effects elicited by LPS-Re, such as the production of interleukin 6 and tumor necrosis factor alpha by macrophages, and the acute lethality in galactosamine-sensitized mice, were not inhibited by E1. The results suggest that the specificity of the LPS receptor which triggers the production of cytokines in macrophages is different from that of the LPS receptor which induces activation of pre-B and B lymphocytes, and is also different from that of the major LPS-binding sites of macrophages. This is consistent with the hypothesis that the large majority of LPS-binding sites of macrophages do not trigger cytokine production, and that the small number of "signaling LPS receptors" of macrophages have fine specificities which are different from those of B cells.