Inhibition of Macrophage DNA Synthesis by Immunomodulators

Abstract

Oil-induced guinea pig peritoneal exudate macrophages were found to incorporate actively [3H]thymidine without any tissue fluids such as conditioned medium, lymphokines or inflammatory tissue exudates. The [3H]thymidine incorporation was markedly suppressed by macrophage stimulants such as muramyl dipeptide (MDP) or bacterial lipopolysaccharide (LPS), while glucosamine incorporation was simultaneously increased by these stimulants. The degree of suppression of thymidine incorporation depended on the cell density, the concentrations of the stimulants, and sera or culture media used. The exposure of macrophages to MDP for 30 min was sufficient to cause significant suppression.A muramyl dipeptide (MDP), N-acetylmuramyl-L-alanyl-n-isoglutamine, a structure essential for immunoregulatory capacity of bacterial cell walls (2), has been found to activate macrophages when measured with different parameters, including enhanced macrophage spreading on and attachment to glass or plastic surfaces (7). Concerning the finding that MDP increased the number of macrophages attached to substrata, we felt it necessary to exclude the possibility that the increase of attached macrophages might reflect, at least partly, a possible increase in the number of macrophages caused by a MDP-stimulated proliferation. Therefore, we studied the effect of MDP on thymidine incorporation into macrophages and found that MDP did not increase but rather decreased the incorporation (7). In the present study we confirmed and extended this finding.

The Synthetic Immunomodulator Murabutide Controls Human Immunodeficiency Virus Type 1 Replication at Multiple Levels in Macrophages and Dendritic Cells

“…The proliferative activity of MDMs was not significantly modified (P Ͼ 0.05) by treatment with Murabutide (1,123 Ϯ 212 on day 2 and 1,150 Ϯ 207 on day 6). This is in contrast to the effects of other immunomodulators, including LPS, which have been reported to inhibit macrophage DNA synthesis (42).…”

Granuloma Formation by Muramyl Dipeptide Associated with Branched Fatty Acids, a Structure Probably Essential for Tubercle Formation by Mycobacterium tuberculosis

“…We recently found that DNA replication of macrophages was markedly inhibited when the macrophages were activated by MDP (22). This fact suggests that MDP stimulates macrophages to differentiate into epithelioid cells (this possibility will be discussed in more detail separately).…”