ISOLATION OF A MACROPHAGE-LIKE CELL-LINE DEFECTIVE IN BINDING OF LIPOPOLYSACCHARIDE - INFLUENCE OF SERUM AND LIPOPOLYSACCHARIDE CHAIN-LENGTH ON MACROPHAGE ACTIVATION

A mutant cell line (J7.DEF.3) derived from murine macrophage-like J774 .1 cells, was isolated on the basis of defective specific I-125-labele d LPS-binding in the presence of serum. Although J7.DEF.3 cells still respond to LPS in inducing TNF-alpha release and nitric oxide (NO) for mation, these cells nevertheless showed significantly decreased respon siveness to LPS relative to the J774.1 parent. Under serum-free condit ions, no differences between J774.1 and J7.DEF.3 cells in response to LPS were observed. The time kinetics of responsiveness to LPS also sho wed a delay in the onset of TNF-alpha release and NO formation in the mutant cells relative to parent cells. importantly, this decrease in r esponsiveness to LPS relative to parental cells was dependent on the l ength of the polysaccharide portion of LPS. The defect in the mutant c ells has been shown to be specific for LPS, in that these cells respon d to heat-killed Listeria monocytogenes and to zymosan to a similar ex tent as do the parental cells. Collectively these results suggest that the defect in the J7.DEF.3 mutant cells may be related to a cellular LPS-binding molecule that, in turn, may depend upon an LPS-binding ser um component.