Macrophages are stimulated by muramyl dipeptide to induce polymorphonuclear leukocyte accumulation in the peritoneal cavities of guinea pigs

Nagao, Shigeki; Nakanishi, Michie; Kutsukake, Hiroshi; Yagawa, Katsuro; Kusumoto, Shoichi; Shiba, Tetsuo; Tanaka, Atsushi; Kotani, Shozo

doi:10.1128/iai.58.2.536-542.1990

Cited by 18 publications

(4 citation statements)

References 28 publications

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“…Apart from exerting antibacterial activity following infusion of alkaloids which decimated the intensity of sub-clinical mastitis, it mediated enhancement of somatic cell infiltration in the milk suggesting chemoattractant property of the alkaloids. These findings are consistent with previous studies in cows treated with some biological response modulator (De and Mukherjee 2013), or with cell wall product of Mycobacterium phlei in bovine SCM (Mukherjee et al 2004) and in guinea pigs treated with peptidoglycan subunit by intraperitoneal route (Nagao et al 1990).…”

Section: Discussionsupporting

confidence: 93%

Immunomodulation of IL-1, IL-6 and IL-8 cytokines by Prosopis juliflora alkaloids during bovine sub-clinical mastitis

et al. 2018

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The current work is focused on establishing therapeutic protocol using unconventional drugs of herbal origin and studying their mechanism of action at molecular level in the treatment of bovine sub-clinical mastitis. It explores the potential of different cytokines which can be used for diagnosis, prognosis and monitoring of bovine sub-clinical mastitis. alkaloids was administered intramammarily in 24 sub-clinically affected quarters once a day for 5 consecutive days at the rate of 10 ml of 1% formulation. In 18 disease control quarters, sterile normal saline was infused. The bacterial cultural examination, somatic cell count (SCC) and cytokines (IL-1β, IL-6, IL-8, IL-12, GM-CSF, IFN-γ, TNF-α) expression by real-time PCR were evaluated on day 7, 14, 21 and 28 post-last treatment from milk samples. Around 75.0% of treatment group quarters showed significant ( < 0.05) reduction in SCC on day 28 post-last treatment, whereas 94.4% control group quarters did not show any significant decline in SCC. 58.3% of treated quarters showed both bacteriological cure as well as significant ( < 0.05) reduction in SCC on day 28 post-last treatment. While, among control group quarters, 83.3% quarters not only remained bacteriological positive, they also did not show any significant decline in SCC. The in vitro antimicrobial activity of alkaloids of was evaluated. Lower concentrations of alkaloids (0.25% and 0.50%) dissolved in normal saline showed zone of inhibition against 12 out of 15 isolates, however higher concentration (1, 1.5, 2, 2.5 and 5%) showed zone of inhibition against all 15 bacterial isolates. The gene expression level of IL-1β, IL-8 and IFN-γ cytokines exhibited significant difference between healthy and sub-clinically affected quarters highlighting the potential of these cytokines in the diagnosis of bovine sub-clinical mastitis. Down-regulation of IL-1, IL-6, IL-8 and IFN-γ cytokines in treated quarters can be explored for making the prognosis and monitoring post-treatment disease progression of bovine sub-clinical mastitis. The alkaloid demonstrated strong in vitro and in vivo antibacterial activity, along with causing immunomodulation by enhancing post-treatment gene expression of IL-1, IL-6 and IL-8 cytokines. Therefore, alkaloids hold a strong claim as an effective alternative herbal therapy in bovine sub-clinical mastitis.

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Section: Discussionsupporting

confidence: 93%

Immunomodulation of IL-1, IL-6 and IL-8 cytokines by Prosopis juliflora alkaloids during bovine sub-clinical mastitis

et al. 2018

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“…We have previously shown that guinea pigs exposed to aerosols of MDP microparticles (MPs) lead to morphological changes in AMΦ like pseudopodia formation and spreading (15). Nagao et al had targeted MDP to peritoneal macrophages (MΦs) in guinea pigs and showed that it induced activation (16). AMΦ are the first line of defense to inhaled foreign antigens.…”

Section: Introductionmentioning

confidence: 99%

Screening for Potential Adjuvants Administered by the Pulmonary Route for Tuberculosis Vaccines

Wang

Muttil

et al. 2009

AAPS J

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Tuberculosis (TB) infects one third of the world's population, and new infections occur at a rate of 1/s. Better vaccines are needed than the live mycobacterium Bacille Calmette-Guérin (BCG). Alveolar macrophages (AMPhis) play a central role in pulmonary manifestations of TB. Targeting immunomodulators to AMPhis, the first line of defense against Mycobacterium tuberculosis (Mtb), may initiate a potent cell-mediated immune response. Muramyl dipeptide (MDP) and trehalose dibehenate (TDB) have elicited strong immune response when delivered to the lungs as aerosols. AMPhis show toxicity in response to some immunomodulators. The objective of this work was to screen the immunomodulators MDP and/or TDB encapsulated in microparticles (MPs) and to evaluate certain indicators of toxicity in human AMPhi-like cells. Poly(lactide-co-glycolide) (PLGA) MPs containing MDP and/or TDB were prepared by spray-drying. The morphology, particle size distribution, and immunomodulator encapsulation efficiency of MPs were examined. THP-1 cells were exposed to these MPs for 24 h and characteristics of cell morphology, tumor necrosis factor-alpha (TNF-alpha) release, lactate dehydrogenase (LDH), N-acetyl-beta-D: -glucosaminidase (NAG) and alkaline phosphatase (ALP) activity in AMPhi culture supernatants were measured. MTT assay was used to assess the viability of cells. Spray-drying produced low-density MPs having volume median diameters between 4 and 6 microm as measured by laser diffraction and projected area diameter between 3 and 5 microm calculated by microscopy. More TNF-alpha was produced by THP-1 cells exposed to MPs composed of PLGA-MDP or PLGA alone than PLGA-TDB. LDH release following exposure to MPs of PLGA-MDP and PLGA alone was greater than controls. NAG release was higher following exposure to MPs of PLGA alone or PLGA-MDP 0.1% than PLGA-TDB (0.1% and 1.0%). Cells remained viable after exposure to MPs as per MTT assay. PLGA-MDP MPs demonstrated statistically elevated indicators of biochemical responses in cell culture compared to PLGA-TDB MPs, but the extent of their potential to elicit adverse effects in vivo must be studied independently.

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“…BPLP‐PLA nanoparticles were fabricated by a single emulsion method . In order to increase THP‐1 cell targeting efficiency, we further modified drug‐laden nanoparticles with MTP, which has macrophage immuno‐potentiating effects without significant cytotoxicity . MTP was successfully conjugated with BPLP‐PLA and BPLP‐PLA‐PLX4032 nanoparticles by carbodiimide chemistry, as confirmed by Fourier transform infrared spectroscopy (FTIR) (Figure S1, Supporting Information).…”

Section: Resultsmentioning

confidence: 94%

Immune Cell‐Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery

Xie

Kim

et al. 2016

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Although tremendous efforts have been made on targeted drug delivery systems, current therapy outcomes still suffer from low circulating time and limited targeting efficiency. The integration of cell-mediated drug delivery and theranostic nanomedicine can potentially improve cancer management in both therapeutic and diagnostic applications. By taking advantage of innate immune cell’s ability to target tumor cells, we developed a novel drug delivery system by using macrophages as both nanoparticle-carriers and navigators to achieve cancer-specific drug delivery. Theranostic nanoparticles were fabricated from a unique polymer, biodegradable photoluminescent poly (lactic acid) (BPLP-PLA), which possesses strong fluorescence, biodegradability, and cytocompatibility. In order to minimize the toxicity of cancer drugs to immune cells and other healthy cells, an anti-BRAF V600E mutant melanoma specific drug (PLX4032) was loaded into BPLP-PLA nanoparticles. Muramyl tripeptide (MTP) was also conjugated onto the nanoparticles to improve the nanoparticle loading efficiency. The resulting nanoparticles were internalized within macrophages, which were tracked via the intrinsic fluorescence of BPLP-PLA. Macrophages carrying nanoparticles delivered drugs to melanoma cells via cell-cell binding. Pharmacological studies also indicated that the PLX4032 loaded nanoparticles effectively killed melanoma cells. Our “self-powered” immune cell-mediated drug delivery system demonstrates a potentially significant advancement in targeted theranostic cancer nanotechnologies.

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Macrophages are stimulated by muramyl dipeptide to induce polymorphonuclear leukocyte accumulation in the peritoneal cavities of guinea pigs

Cited by 18 publications

References 28 publications

Immunomodulation of IL-1, IL-6 and IL-8 cytokines by Prosopis juliflora alkaloids during bovine sub-clinical mastitis

Immunomodulation of IL-1, IL-6 and IL-8 cytokines by Prosopis juliflora alkaloids during bovine sub-clinical mastitis

Screening for Potential Adjuvants Administered by the Pulmonary Route for Tuberculosis Vaccines

Immune Cell‐Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery

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