title: Comparative study of the effects of peptidoglycan monomer and structurally related adamantyltripeptides on humoral immune response to ovalbumin in the mouse.
abstract: Peptidoglycan monomer, GlcNAc-MurNAc-L-Ala-D-isoGln-mesoDAP(omega NH2)-D-Ala-D-Ala (PGM) originating from Brevibacterium divaricatum and synthetic adamantyltripeptides, diastereoisomers of D,L-(adamant-2-yl)-Gly-L-Ala-D-isoGln (AdTP1 and AdTP2) exhibit immunomodulating activity. An experimental model in the mouse has been established with suboptimal amounts of ovalbumin (OVA) as the immunogen, and parallel testing of adjuvant activity of these three immunomodulators was carried out in Balb/c, C57B16 or CBA mice. Tested compounds (100 or 200 micrograms/mouse) mixed with OVA in saline (50 micrograms/mouse) were administered s.c. Anti-OVA was assayed by ELISA in the sera of mice taken 7 days after the boosters (given on days 14 and 28). The treatment with PGM and one of the diastereoisomers, AdTP2, resulted in significantly higher increase in anti-OVA IgG levels (stimulation index up to 46) with respect to controls and groups treated with AdTP1. The effect of AdTP2 treatment was comparable to that of PGM in most experiments after the first booster, but after the second booster PGM exhibited markedly better effect. PGM and AdTP2 also induced markedly higher levels of IgG1 and IgG2 anti-OVA subclasses than detected in controls and AdTP1 treated mice, indicating that these two immunomodulators might upregulate both Th1-like and Th2-like immune responses.
authors.affiliation: Institute of Immunology, Zagreb, Croatia. jelka.tomasic@imz.tel.hr
authors.forename: J
authors.initials: J
authors.lastname: Tomasić
authors.forename: I
authors.initials: I
authors.lastname: Hanzl-Dujmović
authors.forename: B
authors.initials: B
authors.lastname: Spoljar
authors.forename: B
authors.initials: B
authors.lastname: Vranesić
authors.forename: M
authors.initials: M
authors.lastname: Santak
authors.forename: A
authors.initials: A
authors.lastname: Jovicić
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000145:classification; D007075:Immunoglobulin M / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009842:Oligopeptides / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D010457:Peptidoglycan; D013237:Stereoisomerism
chemical_list: C405426:(adamant-2-yl)-glycyl-alanyl-isoglutamine; D000276:Adjuvants, Immunologic; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009842:Oligopeptides; D010457:Peptidoglycan; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C032972:peptidoglycan pentapeptide-mDap3; D010047:Ovalbumin; D000218:Adamantane