Role of plasma, lipopolysaccharide-binding protein, and CD14 in response of mouse peritoneal exudate macrophages to endotoxin

Plasma lipopolysaccharide (LPS)-binding protein (LBP) and membrane CD14 fun ction to enhance the responses of monocytes to low concentrations of endoto xin. Surprisingly, recent reports have suggested that LBP or CD14 may be di spensable for macrophage responses to low concentrations of LPS or may even exert an inhibitory effect in the case of LBP. We therefore investigated w hether LBP and CD14 participated in the response of mouse peritoneal exudat e macrophages (PEM) to LPS stimulation. In the presence of a low amount of plasma (<1%) or of recombinant mouse or human LBP, PEM were found to respon d to low concentrations of LPS (<5 to 10 ng/ml) in an LBP- and CD14-depende nt manner. However, tumor necrosis factor production (not interleukin-6 pro duction) by LPS-stimulated PEM was reduced when cells were stimulated in th e presence of higher concentrations of plasma or serum (5 or 10%). Yet, the inhibitory effect of plasma or serum was not mediated by LBP. Taken togeth er with previous results obtained with LBP and CD14 knockout mice in models of experimental endotoxemia, the present data confirm a critical part for LBP and CD14 in innate immune responses of both blood monocytes and tissue macrophages to endotoxins.