Lipopolysaccharide enhancement of colony-stimulating factor-1 induced monocytopoiesis

This investigation examines the effects of bacterial lipopolysaccharide (LPS) on the proliferative response of murine femoral bone marrow myeloid precursors induced by colony-stimulating factor-1. This proliferative response was measured both as [³H]- thymidine incorporation in liquid culture and colony formation in semisolid agar. Lipopolysaccharide exposure produced dose-dependent effects on CSF-induced myeloid proliferation, ranging from significant suppression (p ≤ 0.01) at LPS concentrations greater than 10^-1 mcg/ml to significant enhancement (p ≤ 0.01) at 10 ^-3 to 10 ^-5 meg LPS/ml. Similar LPS-induced enhancement occurred both in the presence and absence of anti-IFN (α + β) antiserum and indomethacin, thus the LPS effect was independent of CSF-induced interferon and prostaglandin E. Enhancement was not due to LPS-stimulated CSF production, as proliferation was not observed in cultures receiving LPS alone. The lack of LPS-induced enhanced proliferation by LPS-hyporesponsive C3H/HeJ cells indicated enhancement is due to lipid A. Removal of more mature adherent cells via plating did not prevent the LPS stimulation effect, nor did co-culture of C3H/HeJ and LPS-responsive C3H/AnF nonadherent cells result in proliferation more than additive with respect to proliferation seen in cultures incubated separately. These results indicated that LPS acts directly on myeloid precursors and not via a secondary soluble mediator produced by LPS-stimulated cells. Finally, the ability of contaminating serum endotoxin to mask the stimulatory effects of experimentally administered nanogram levels of LPS is presented.