In Vivo and in Vitro Stimulation of Nonspecific Immunity by the -D-p-Aminophenyl Glycoside of N-Acetylmuramyl-L-Alanyl-D-Isoglutamine and an Oligomer Prepared by Cross-Linking with Glutaraldehyde

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Abstract
Several biological activities of N-acetylmuramyl-l-alanyl-d-isoglutamine (MDP for muramyl dipeptide), a synthetic immunoadjuvant, are inhibited after glycosidation with p-aminophenol. Thus, this glycoside does not induce an increased humoral antibody response in mice when injected in saline, although it retains its stimulatory effect on circulating antibodies and delayed hypersensitivity after administration in a water-in-oil emulsion. The capacity of MDP to stimulate mouse spleen cells is lost, and, moreover, the analogue is unable to increase nonspecific resistance to infection under conditions where MDP is active. After cross-linking of the β-d-p-aminophenyl glycoside of MDP with glutaraldehyde, several biological activities of MDP are recovered. Moreover, the cross-linked oligomer (molecular weight, ∼6,000 daltons) is able to stimulate the uptake of thymidine by spleen cells from a strain of mice weakly responsive to MDP and is more active than MDP in protecting mice against bacterial challenge.