Immunostimulatory activity of 1-O-acylated muramyl dipeptides, with or without a 6-O-phosphoryl group, in aqueous form.
Immunostimulatory effects of 1-O-acylated derivatives of N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP) methyl ester, with or without the 6-O-phosphoryl group, on augmentation of IgG antibody response against influenza hemagglutinin (HA) vaccine, in vivo macrophage activation and enhancement of non-specific host resistance against Pseudomonas aeruginosa infection were investigated. The activities were tested intraperitoneally (i.p.) in mice administered test samples solubilized or suspended in saline. The introduction of longer chain acyl groups into MDP methyl esters significantly induced enhancement of the IgG antibody response. Among them, the adjuvant activity of 1-O-linked 2-tetradecylhexadecanoyl (B30)-MDP methyl ester was comparable to that of 6-O-B30-MDP used as a positive control. Phosphorylation at the C6 position of the acylated MDP analogs did not induce a significant increment in the activity. With respect to phagocytic, cellular acid phosphatase and cytostasis-inducing activities, i.p. administration of acylated MDP analogs caused significant increment and activation of peritoneal macrophages. The cytostasis-inducing activity of 1-O-octadecanoyl- or 1-O-B30-MDP methyl ester with or without a phosphoryl group was more intensive than that of 6-O-B30-MDP. Acylated MDP analogs enhanced non-specific resistance against P. aeruginosa infection when the analogs were administered i.p. on the day before the infection. The enhancement was closely related to the accumulation of polymorphonuclear cells in the peritoneal cavity. The manifestation of these immunostimulatory activities by 1-O-acylated MDP analogs depended closely on the increasing carbon chain length of fatty acid substituents when administered in aqueous form.
Furuya
T
T
School of Hygienic Sciences, Kitasato University, Kanagawa, Japan.
Kumazawa
Y
Y
Takimoto
H
H
Nagumo
T
T
Nagamine
T
T
Aizawa
C
C
Mizunoe
K
K
Kiso
M
M
Hasegawa
A
A
Nomoto
K
K
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006385:Hemagglutination Inhibition Tests; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis; D007252:Influenza Vaccines / Q000276:immunology; D008262:Macrophage Activation; D051379:Mice; D010529:Peritoneal Cavity / Q000166:cytology; D011552:Pseudomonas Infections / Q000276:immunology; D011550:Pseudomonas aeruginosa; D013329:Structure-Activity Relationship
D007074:Immunoglobulin G; D007252:Influenza Vaccines; D000119:Acetylmuramyl-Alanyl-Isoglutamine