Disease relevance of Monophosphoryl lipid A

• We examined the capacities of rough mutant Salmonella typhimurium LPS (Rc) and LPS partial structures lipid A, monophosphoryl lipid A (MPLA), lipid IVA, and lipid X to induce production of TNF in whole blood [1].
• We examined the effect of a new adjuvant consisting of purified mycobacterial cell wall skeleton (CWS) and monophosphoryl lipid A (MPL) on the immunogenicity of a murine melanoma vaccine [2].
• Effect of cell wall skeleton and monophosphoryl lipid A adjuvant on the immunogenicity of a murine B16 melanoma vaccine [2].
• Moderate but acceptable transient local reactogenicity was noted at high doses of the vaccine formulation, but little or no systemic toxicity was seen despite liposomal monophosphoryl lipid A doses up to 2200 micrograms [3].
• CD8 cytotoxicity specific for HSV-2 IE proteins was enhanced by 48-67% when CD8 CTLs were coincubated with the combination of monophosphoryl lipid A and QS21 adjuvants at the time of Ag presentation [4].

High impact information on Monophosphoryl lipid A

• Whereas mice exhibited a limited antibody response to immunization with newly emerged Plasmodium falciparum gametes in Freund's adjuvant, all five congenic mouse strains responded to several transmission-blocking vaccine candidate antigens, when parasites were emulsified in a monophosphoryl lipid A (MPL) and trehalose dimycolate (TDM) adjuvant [5].
• In comparison to Freund's complete adjuvant, cell wall skeleton plus monophosphoryl lipid A (CWS:MPL) induced fewer cutaneous toxic effects and stronger antibody and DTH responses but resulted in no greater in vitro cytotoxicity or tumor-protective immunity [2].
• A potent adjuvant monophosphoryl lipid A triggers various immune responses, but not secretion of IL-1beta or activation of caspase-1 [6].
• Vaccination with LTK63/Ag85B-ESAT-6 gave a strong and sustained Th1 response mediated by IFN-gamma-secreting CD4 cells, which led to long-lasting protection against tuberculosis, equivalent to that observed with bacillus Calmette-Gu??rin (BCG) or Ag85B-ESAT-6 in dimethyldioctadecylammonium bromide/monophosphoryl lipid A [7].
• Monophosphoryl lipid A activates both human dendritic cells and T cells [8].

Chemical compound and disease context of Monophosphoryl lipid A

• Structure of the monophosphoryl lipid A moiety obtained from the lipopolysaccharide of Chlamydia trachomatis [9].
• Endotoxin extracted from the heptose-less mutant of Salmonella typhimurium was hydrolyzed in 0.1 N HCl in methanol/water (1:1, v/v) at 100 degrees C to yield lipid A, which was then fractionated on a Sephadex LH-20 column to yield a major monophosphoryl lipid A fraction [10].
• In order to remove any possible effect of E. coli LPS present in IB, the FP was further purified by SDS-PAGE and incorporated into liposomes, either alone or in combination with the adjuvants monophosphoryl lipid A or muramyl dipeptide [11].
• Recently, a relatively nontoxic monophosphoryl Lipid A (LAM) that retains many of the immunobiologic properties of LPS has been isolated from a polysaccharide deficient Re mutant strain of Salmonella minnesota (R595) [12].
• We have evaluated activated alpha2-macroglobulin (alpha2M*) and a squalene-based stable emulsion containing monophosphoryl lipid A (MPL-SE) with granulocyte-macrophage colony stimulating factor (GM-CSF) as adjuvants to enhance the immunogencity of candidate HIV immunogens [13].

Biological context of Monophosphoryl lipid A

• However, acid hydrolysis of the labile phosphate group of the native diphosphorylated lipid A to form monophosphoryl lipid A rendered the molecule ineffective in suppressing scavenger receptor activity [14].
• Rapid phosphorylation of a human platelet protein of Mr 40,000-47,000 (P47), a substrate for protein kinase C activation, preceded secretion of serotonin when platelets were triggered by the most active heptaacyl MLA ion, m/z 1953 [15].
• These results indicate that the degree of acylation of monophosphoryl Lipid A determines its functional properties toward human platelets in regard to secretion of [14C]serotonin, aggregation, and activation of protein kinase C.(ABSTRACT TRUNCATED AT 400 WORDS)[15]
• When congenic mice differing in MHC haplotype were immunized with MSP-1 either in CFA or incorporated into a synthetic monophosphoryl lipid A (LA-15-PH)-liposome formulation, mice of different haplotypes produced anti-MSP-1 Abs capable of inhibiting P. falciparum growth [16].
• Monophosphoryl lipid A stimulated up-regulation of reactive oxygen intermediates in human monocytes in vitro [17].

Anatomical context of Monophosphoryl lipid A

• In this study, we have investigated the effects of monophosphoryl lipid A (MPL) on human monocyte-derived DC as well as peripheral blood T cells [8].
• Pulmonary and hepatic gene expression following cecal ligation and puncture: monophosphoryl lipid A prophylaxis attenuates sepsis-induced cytokine and chemokine expression and neutrophil infiltration [18].
• Lipopolysaccharide (LPS) and the nontoxic derivative of lipid A, monophosphoryl lipid A (MPL), were employed to assess the relationship between expression of LPS-inducible inflammatory genes and the induction of tolerance to LPS in murine macrophages [19].
• Differential sensitivity of CD8+ suppressor and cytotoxic T lymphocyte activity to bacterial monophosphoryl lipid A [20].
• A detoxified derivative of endotoxic lipopolysaccharides (LPS), monophosphoryl lipid A (MPL), which is capable of inducing nonspecific resistance against several infectious organisms, was tested for its capacity to activate peritoneal macrophages (M phi) from young and immunodeficient aging BALB/c and C3H/HeN mice [21].

Associations of Monophosphoryl lipid A with other chemical compounds

• The effect of adjuvants on the specificity of immune responses to the Plasmodium falciparum gp195 protein was investigated using adjuvant formulations based on synthetic muramyl dipeptide and monophosphoryl lipid A derivatives, in parallel with CFA and alum [22].
• Evaluation of monophosphoryl lipid A (MPL) as an adjuvant. Enhancement of the serum antibody response in mice to polysaccharide-protein conjugates by concurrent injection with MPL [23].
• Experimental autoimmune sialoadenitis was induced in PL/J (H-2u) mice by intradermal immunization with human carbonic anhydrase II (CAII) and adjuvant containing monophosphoryl lipid A and trehalose diorynomycolate [24].
• Inoculation of mice with cholesterol-rich liposomes containing the adjuvant monophosphoryl lipid A results in the production of antiserum containing IgM Ab to cholesterol [25].
• Reactivity with native protein was considerably enhanced by incorporation of the adjuvant monophosphoryl lipid A into the liposome or micelle preparations [26].

Gene context of Monophosphoryl lipid A

• Lipopolysaccharide and monophosphoryl lipid A differentially regulate interleukin-12, gamma interferon, and interleukin-10 mRNA production in murine macrophages [27].
• IL-6 concentrations (100 +/- 91 vs. 268 +/- 171 pg/ml; p < .05) and IL-8 concentrations (136 +/- 86 vs. 632 +/- 323 pg/mL; p < .05) elicited by endotoxin challenge were also significantly reduced by monophosphoryl lipid A pretreatment [28].
• The T cell proliferation observed in the presence of nanoparticulate MUC1 and MPLA pulsed-DCs was much higher than DCs pulsed with soluble antigen (P<0.0005) [29].
• P. gingivalis lipid A induced lower production of interleukin-1 beta (IL-1 beta) in splenic macrophage cultures and exhibited a comparable IL-6 producing activity in splenic B cells of C3H/HeN mice as compared to Escherichia coli-type synthetic lipid A (compound 506) and monophosphoryl lipid A from Salmonella minnesota Re 595 (MLA) [30].
• Muramyl dipeptide or monophosphoryl lipid A pretreatment of animals prior to CLP was ineffective in altering the expression of TNF alpha and I-A alpha mRNA [31].

Analytical, diagnostic and therapeutic context of Monophosphoryl lipid A

• The combined approach described here (i.e., vaccination with irradiated syngeneic tumor cells plus MPLA in Cy-pretreated mice) was also shown to be effective in augmenting the serologic response against two additional murine leukemia virus-negative sarcomas that are known to be less immunogenic, CMS4 and CMS5 [32].
• The monophosphoryl lipid A was further fractionated by preparative thin layer chromatography [10].
• Novel approaches to immunotherapy currently being explored include the use of adjuvants, such as monophosphoryl lipid A or nucleotide immunostimulatory sequences derived from bacteria that potentiate T(H)1 responses [33].
• OBJECTIVES: Monophosphoryl lipid A (MLA), a detoxified derivative of the lipid A portion of the endotoxin molecule, given as a pretreatment 24 h prior to cardiac ischemia/reperfusion reduces myocardial stunning and infarction in dogs [34].
• The vaccine was formulated in liposomes with either a low or high dose of 3-deacylated monophosphoryl lipid A (MPL) and administered with alum by intramuscular injection [35].

References