Lipopolysaccharide, muramyl dipeptide and polyinosinic: polycytidylic acid induce the accumulation of inositol phosphates in blood monocytes and lymphocytes.
Rabbit macrophages (Mø) and lymphocytes (Ly) incubated with three structurally dissimilar immunomodulators, lipopolysaccharide (bacterial endotoxin, LPS), polyinosinic: polycytidylic acid (poly-I:C) and muramyl dipeptide (MDP), were found to accumulate inositol phosphates (IPs) in a concentration- and time-dependent manner. The threshold concentration of LPS necessary for an increase in IPs in both cell types was less than 1 ng/ml and a maximum effect was observed between 1 and 10 micrograms/ml. The threshold concentrations for poly-I:C and MDP were between 0.1 and 1 microgram/ml for both cell types. Significant increases in the concentration of inositol phosphates occurred between 30 and 60 min after challenge of either cell type with any of the three agents studied. In addition, all three immunomodulators produced a greater accumulation of IPs in macrophages than in mixed lymphocytes and after 2 h appeared to approach a maximum in macrophages, whereas the IPs level in lymphocytes appeared to be still rising after 2 h. In Mø and Ly the IPs level was increased within 10 min of incubation in the presence of either PGE2 or medium previously obtained from cells incubated with LPS. In addition, anisomycin (a protein synthesis inhibitor) and ketoprofen (a cyclo-oxygenase inhibitor) inhibited the LPS-stimulated increase of IPs accumulation in both cell types. These two observations suggest that the LPS-stimulated increase in IPs in macrophages and lymphocytes is mediated by a protein intermediate and possibly a prostanoid.