Antimicrobial activity of antiproteinases

2002 ◽  
Vol 30 (2) ◽  
pp. 111-115 ◽  
Author(s):  
J.-M. Sallenave
Keyword(s):  
Gene Transfer ◽  
Molecular Mass ◽  
Neutrophil Elastase ◽  
Antimicrobial Properties ◽  
Specific Inhibitor ◽  
Antimicrobial Activities ◽  
Viral Gene ◽  
Transfer Vectors

Low-molecular-mass neutrophil elastase inhibitors have been shown to be important in the control of lung inflammation. In addition to inhibiting the enzyme neutrophil elastase, these low-molecular-mass compounds (10 kDa) have been shown to have other activities. For example, secretory leucocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor/SKALP (skin-derived antileucoproteinase)/elafin have also been shown to have ‘defensin’-like antimicrobial activities. Indeed, these inhibitors have antimicrobial properties in vitro against bacteria, fungi and, potentially, HIV. In addition, we have shown, using an adenovirus-mediated gene transfer overexpression strategy, that elafin is also active against Pseudomonas aeruginosa infection in mice in vivo. The mechanism of action is currently under investigation. In addition to these direct or indirect effects on microbes, it has been shown that lipopolysaccharide is able to up-regulate SPLI production in macrophages in vitro, and that the addition of recombinant SLPI to human monocytes or the transfection of macrophages with SPLI can down-regulate pro-inflammatory mediators such as tumour necrosis factor, presumably to limit self-damaging excessive inflammation. Using viral gene transfer vectors, we are currently investigating the potential of these inhibitors in various models of inflammation in vivo.

scholarly journals Antimicrobial, antioxidant activities and toxicity on Cavia porcellus of Dialium angolense Welw. Ex Oliv, a traditional medicinal plant from Bagira in Eastern of DR Congo

2020 ◽  
Vol 13 (2) ◽  
pp. 166-180
Author(s):  
Bashige Chiribagula V ◽  
Bakari Amuri S ◽  
Okusa Ndjolo Philippe ◽  
Kahumba Byanga J ◽  
Duez P ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Acute Toxicity ◽  
Antioxidant Activities ◽  
Antimicrobial Properties ◽  
Salmonella Typhi ◽  
Antimicrobial Activities ◽  
Cavia Porcellus ◽  
E Coli

Dialium angolense is used in Bagira for its various medicinal properties particularly in the management of infectious diseases. In this study, the methanol and aqueous extracts of leaves and fruits were evaluated for their in vitro antioxidant and antimicrobial properties and their in vivo toxicity on Cavia porcellus. The major phytochemical classes of extracts were screened using standard in-tube reactions. The antimicrobial study was tested on Candida albicans, Escherichia coli, Salmonella typhi, Staphylococcus aureus and Streptococcus pneumoniae using agar well diffusion and dilution methods, while the antioxidant activity was evaluated by a DPPH assay. For the acute toxicity study, animals (6/group) were orally given in a single dose 5000, 1000 or 15000 mg of extract/kg body weight (BW) then observed for 14 days. In sub-acute toxicity assays, 150 or 300 mg/kg BW/day were orally given, and animals observed for 28 days. Total phenolics and total flavonoids contents ranged 1.19 to 1.61 mg GAE.g-1 and 0.45 to 1.01 mg QEg-1, respectively. The extracts presented antioxidant activity with IC50 ranging 4.9 to 6.9 µg/mL. The minimal inhibitory concentration (MIC) on tested strains ranged from 1.9 to 500 µg/mL with the aqueous extract of fruits as a most active extract: MIC=1.9 µg/mL on E. coli and C. albicans. No signs of toxicity were noted during the acute and sub-acute toxicity assessments, suggesting a maximal tolerate doses (MDT) and LD50 > 15000 mg/kg BW. This study highlights the antioxidant and antimicrobial activities of Dialium angolense and suggests that further studies be directed towards the isolation of active compounds.

scholarly journals Effects of human neutrophil elastase (HNE) on neutrophil function in vitro and in inflamed microvessels

Blood ◽  
1993 ◽  
Vol 82 (7) ◽  
pp. 2188-2195 ◽  
Author(s):  
RC Woodman ◽  
PH Reinhardt ◽  
S Kanwar ◽  
FL Johnston ◽  
P Kubes
Keyword(s):  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Neutrophil Migration ◽  
Specific Inhibitor ◽  
Neutrophil Infiltration ◽  
Cathepsin G ◽  
Neutrophil Adhesion ◽  
Human Neutrophil Elastase

Abstract The primary objective of this study was to test the hypothesis that human neutrophil elastase (HNE) affects neutrophil infiltration (adhesion and emigration) into inflamed vessels. To determine whether HNE contributes to neutrophil adhesion in vivo, intravital microscopy was used to study neutrophil-endothelial cell interactions in single inflamed postcapillary venules. Superfusion of platelet-activating factor (PAF) (100 nmol/L) onto the mesentery caused an increase in neutrophil-neutrophil interactions, neutrophil adhesion to postcapillary venules, and cellular emigration out of the vasculature. Both L658 758 (an elastase-specific inhibitor), and Eglin C (an elastase and cathepsin G inhibitor) significantly attenuated all of these parameters in vivo. To further characterize the mechanism(s) involved, various in vitro parameters were assessed. HNE, but not trypsin, caused a dose-dependent (0.01 to 1.0 microgram/mL) increase in the expression of the beta subunit (CD18) of the CD11/CD18 adhesive glycoprotein complex on neutrophils. An HNE-dependent increase in CD11b expression was also observed; however, HNE did not affect the expression of other neutrophil adhesion molecules (L-selectin), superoxide production, or degranulation. PAF-enhanced CD18 expression on neutrophils and neutrophil migration were both abolished by L658 758 but PAF-induced neutrophil adhesion to endothelial monolayers was not affected by the antiproteinase. The in vitro data suggest that the antiproteinases do not directly prevent neutrophil adhesion in vivo but may be important in other CD18-dependent events such as neutrophil- neutrophil interaction or neutrophil infiltration (chemotaxis). These results translate into an important, rate-limiting role for elastase in the process of leukocyte infiltration and accumulation in inflamed microvessels.

scholarly journals Effects of human neutrophil elastase (HNE) on neutrophil function in vitro and in inflamed microvessels

Blood ◽  
1993 ◽  
Vol 82 (7) ◽  
pp. 2188-2195
Author(s):  
RC Woodman ◽  
PH Reinhardt ◽  
S Kanwar ◽  
FL Johnston ◽  
P Kubes
Keyword(s):  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Neutrophil Migration ◽  
Specific Inhibitor ◽  
Neutrophil Infiltration ◽  
Cathepsin G ◽  
Neutrophil Adhesion ◽  
Human Neutrophil Elastase

The primary objective of this study was to test the hypothesis that human neutrophil elastase (HNE) affects neutrophil infiltration (adhesion and emigration) into inflamed vessels. To determine whether HNE contributes to neutrophil adhesion in vivo, intravital microscopy was used to study neutrophil-endothelial cell interactions in single inflamed postcapillary venules. Superfusion of platelet-activating factor (PAF) (100 nmol/L) onto the mesentery caused an increase in neutrophil-neutrophil interactions, neutrophil adhesion to postcapillary venules, and cellular emigration out of the vasculature. Both L658 758 (an elastase-specific inhibitor), and Eglin C (an elastase and cathepsin G inhibitor) significantly attenuated all of these parameters in vivo. To further characterize the mechanism(s) involved, various in vitro parameters were assessed. HNE, but not trypsin, caused a dose-dependent (0.01 to 1.0 microgram/mL) increase in the expression of the beta subunit (CD18) of the CD11/CD18 adhesive glycoprotein complex on neutrophils. An HNE-dependent increase in CD11b expression was also observed; however, HNE did not affect the expression of other neutrophil adhesion molecules (L-selectin), superoxide production, or degranulation. PAF-enhanced CD18 expression on neutrophils and neutrophil migration were both abolished by L658 758 but PAF-induced neutrophil adhesion to endothelial monolayers was not affected by the antiproteinase. The in vitro data suggest that the antiproteinases do not directly prevent neutrophil adhesion in vivo but may be important in other CD18-dependent events such as neutrophil- neutrophil interaction or neutrophil infiltration (chemotaxis). These results translate into an important, rate-limiting role for elastase in the process of leukocyte infiltration and accumulation in inflamed microvessels.

scholarly journals Invitro Antimicrobial Activities of Mitracarpus scaber Against Some Common Bacteria of Aquatic Origin

2021 ◽  
Vol 32 (3) ◽  
pp. 119
Author(s):  
Abdullateef Abiodun Ajadi ◽  
Benjamin Emikpe ◽  
Ahmed Akeem
Keyword(s):  
Antimicrobial Properties ◽  
Ethanolic Extract ◽  
Antibacterial Activities ◽  
Antimicrobial Activities ◽  
Phytochemical Analysis ◽  
Ethanolic Extracts ◽  
Zones Of Inhibition ◽  
Mitracarpus Scaber

Some plants have been reported to be of medicinal values and reserve some antimicrobial properties. One of such plants is Mitracarpus scaber and its effect on bacterial growth is evaluated. The study aimed at evaluating the phytochemical analyses and antimicrobial potentials of Mitracarpus scaber against aquatic bacteria including Aeromonas, Bacillus, Vibrio and Staphylococcus Spp. Leaves of Mitracarpus scaber were collected, washed and air dried and phytochemical analysis and antimicrobial investigation of ethanolic and aqueous extracts of the leaves were carried out against a panel of bacteria isolated from diseased catfish from various farms. The phytoconstituents detected include saponins, tannins, flavonoids, tarpenoids, steroids, anthraquinones and alkaloids in both aqueous and ethanolic extracts. Both aqueous and ethanolic extracts of M. scaber showed varying degree of antibacterial activities but ethanolic extract showed a higher activity against the pathogens tested. The ethanolic extract had zones of inhibition similar to that of standard antibiotics (enrofloxacin) across all tested microbes.  The lowest minimum inhibitory concentration of ethanolic extract of M. scaber was against Bacillus sp with 10mg/ml while the highest was 85mg/ml against Staphylococcus species. The results of the assays showed promising evidences that M. scaber is a potential antibacterial agent against aquatic microbes.  However, further studies are recommended to fractionate its constituents and determine the in vitro and in vivo anti-microbial activities and the exact mechanism of action of the constituents.

Induction of antigen-specific CD4+ T-cell anergy and deletion by in vivo viral gene transfer

Blood ◽  
2004 ◽  
Vol 104 (4) ◽  
pp. 969-977 ◽  
Author(s):  
Eric Dobrzynski ◽  
Federico Mingozzi ◽  
Yi-Lin Liu ◽  
Elisabeth Bendo ◽  
Ou Cao ◽  
...  
Keyword(s):  
T Cell ◽  
Gene Transfer ◽  
Cell Receptor ◽  
Cd4 T Cell ◽  
Viral Gene ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Viral Gene Transfer

AbstractImmune responses to the therapeutic gene product are a potentially serious complication in treatment of genetic disease by gene therapy. Induction and maintenance of immunologic hypo-responsiveness to the therapeutic antigen is therefore critical to the success of gene-based treatment of inherited protein deficiency. Here, we demonstrate induction of antigen-specific CD4+ T-cell tolerance to a secreted transgene product (ovalbumin, ova) in ova-specific T-cell receptor (TCR) transgenic mice by hepatic adeno-associated virus (AAV)–mediated gene transfer. Transduced mice maintained stable circulating ova levels without evidence of an immune response. Lymph node cells and splenocytes were hypo-responsive to ova as early as day 10 after gene transfer. Numbers of TCR+CD4+ cells were reduced in secondary lymphoid organs and in the thymus by 1 to 2 months after vector administration. The remaining TCR+CD4+ cell population was anergic to ova antigen in vitro and enriched for CD25+ cells. These data provide direct evidence that transgene expression following in vivo viral gene transfer can induce CD4+ T-cell tolerance to the transgene product, involving anergy and deletion mechanisms.

scholarly journals DNA nuclear targeting sequences for enhanced non-viral gene transfer: An in vitro and in vivo study

2021 ◽  
Author(s):  
Yann T. Le Guen ◽  
Chantal Pichon ◽  
Philippe Guégan ◽  
Kévin Pluchon ◽  
Tanguy Haute ◽  
...  
Keyword(s):  
Gene Transfer ◽  
In Vivo Study ◽  
Viral Gene ◽  
Nuclear Targeting ◽  
Viral Gene Transfer

Synthesis of Novel 3(N,N-dialkylamino)alkyl/phenyl Substituted Thieno [2,3-d]pyrimidinones as H1-Anti-Histaminic and Antimicrobial Agents

2019 ◽  
Vol 15 (1) ◽  
pp. 63-70
Author(s):  
Shiv Dev Singh ◽  
Arvind Kumar ◽  
Firoz Babar ◽  
Neetu Sachan ◽  
Arun Kumar Sharma
Keyword(s):  
Antimicrobial Activity ◽  
Potassium Hydroxide ◽  
Antimicrobial Agents ◽  
Pyrimidine Ring ◽  
Antimicrobial Activities ◽  
Screening Methods ◽  
Chlorpheniramine Maleate ◽  
In Vivo Screening

Background: Thienopyrimidines are the bioisoster of quinazoline and unlike quinazoline exist in three isomeric forms corresponding to the three possible types annulation of thiophene to the pyrimidine ring viz thieno[2,3-d] pyrimidine, thieno[3,2-d] pyrimidine and thieno[3,4-d]pyrimidine. Heterocyclic containing the thienopyrimidinone moiety exhibits various pronounced activities such as anti-hypertensive, analgesic and anti-inflammatory, antiviral, platelet aggregation inhibitory, antiprotozoal bronchodilatory, phosphodiesterase inhibitory, antihistaminic, antipsychotic and antimicrobial activity. Objective: Synthesis of novel 3(N,N-dialkylamino)alkyl/phenyl substituted thieno[2,3-d]pyrimidinones as H1-anti-histaminic and antimicrobial agents. Methods: A series of 3-[(N,N-dialkylamino)alkyl/phenyl]-2-(1H)thioxo-5,6,7,8-tetrahydrobenzo(b) thieno(2,3-d)pyrimidine-4(3H)-ones[4a-d], their oxo analogous [5a-d] and 3-[(N,N-dialkylamino)alkyl]- 2-chlorophenyl-5,6,7,8-tetrahydrobenzo(b)thieno(2,3-d)pyrimidine- 4 (3H)-ones[6a-d]derivative were synthesized from 2-amino-4,5,6,7-tetrahydrobenzo(b)thiophene-3-carboxylic acid by nucleophilic substitution of different N,N-dialkyl alkylene/phenylene diamines on activated 3-acylchloride moiety followed by cyclocondensation with carbon disulfide and ethanolic potassium hydroxide to get [4a-d] and in second reaction by condensation with 4-chlorobenzoyl chloride to get [6a-d] by single pot novel innovative route. The oxo analogous [5a-d] were prepared by treating derivatives [4a-d] with potassium permagnate in ethanolic KOH. The synthesized compound were evaluated for H1-antihistaminic and antimicrobial activities. Results: All synthesized compounds exhibited significant H1-antihistaminic activity by in vitro and in vivo screening methods and data were verified analytically and statistically. The compound 4a, 4b, 5a and 5b showed significant H1-antihistaminiic activity than the reference standard chlorpheniramine maleate. The compound 6d, 6c, 5c and 4c exhibited significant antimicrobial activity.

scholarly journals Targeting Toll-Like Receptor 2: Polarization of Porcine Macrophages by a Mycoplasma-Derived Pam2cys Lipopeptide

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 692
Author(s):  
Giulia Franzoni ◽  
Antonio Anfossi ◽  
Chiara Grazia De Ciucis ◽  
Samanta Mecocci ◽  
Tania Carta ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Macrophage Polarization ◽  
Surface Protein ◽  
Antimicrobial Activities ◽  
Toll Like Receptor ◽  
Activation Markers ◽  
Class I Mhc ◽  
Toll Like Receptor 2

Toll-like receptor 2 (TLR2) ligands are attracting increasing attention as prophylactic and immunotherapeutic agents against pathogens and tumors. We previously observed that a synthetic diacylated lipopeptide based on a surface protein of Mycoplasma agalactiae (Mag-Pam2Cys) strongly activated innate immune cells, including porcine monocyte-derived macrophages (moMΦ). In this study, we utilized confocal microscopy, flow cytometry, multiplex cytokine ELISA, and RT-qPCR to conduct a comprehensive analysis of the effects of scalar doses of Mag-Pam2Cys on porcine moMΦ. We observed enhanced expression of activation markers (MHC class I, MHC class II DR, CD25), increased phagocytotic activity, and release of IL-12 and proinflammatory cytokines. Mag-Pam2Cys also upregulated the gene expression of several IFN-α subtypes, p65, NOS2, and molecules with antimicrobial activities (CD14, beta defensin 1). Overall, our data showed that Mag-Pam2Cys polarized porcine macrophages towards a proinflammatory antimicrobial phenotype. However, Mag-Pam2Cys downregulated the expression of IFN-α3, six TLRs (TLR3, -4, -5, -7, -8, -9), and did not interfere with macrophage polarization induced by the immunosuppressive IL-10, suggesting that the inflammatory activity evoked by Mag-Pam2Cys could be regulated to avoid potentially harmful consequences. We hope that our in vitro results will lay the foundation for the further evaluation of this diacylated lipopeptide as an immunopotentiator in vivo.

scholarly journals Antimicrobial Activity of Curcumin in Nanoformulations: A Comprehensive Review

2021 ◽  
Vol 22 (13) ◽  
pp. 7130
Author(s):  
Jeffersson Krishan Trigo-Gutierrez ◽  
Yuliana Vega-Chacón ◽  
Amanda Brandão Soares ◽  
Ewerton Garcia de Oliveira Mima
Keyword(s):  
Polymeric Nanoparticles ◽  
Graphene Quantum Dots ◽  
Antimicrobial Properties ◽  
Antimicrobial Effect ◽  
Clinical Scenarios ◽  
Low Cytotoxicity ◽  
Bacteria And Fungi ◽  
Drug Resistant Strains

Curcumin (CUR) is a natural substance extracted from turmeric that has antimicrobial properties. Due to its ability to absorb light in the blue spectrum, CUR is also used as a photosensitizer (PS) in antimicrobial Photodynamic Therapy (aPDT). However, CUR is hydrophobic, unstable in solutions, and has low bioavailability, which hinders its clinical use. To circumvent these drawbacks, drug delivery systems (DDSs) have been used. In this review, we summarize the DDSs used to carry CUR and their antimicrobial effect against viruses, bacteria, and fungi, including drug-resistant strains and emergent pathogens such as SARS-CoV-2. The reviewed DDSs include colloidal (micelles, liposomes, nanoemulsions, cyclodextrins, chitosan, and other polymeric nanoparticles), metallic, and mesoporous particles, as well as graphene, quantum dots, and hybrid nanosystems such as films and hydrogels. Free (non-encapsulated) CUR and CUR loaded in DDSs have a broad-spectrum antimicrobial action when used alone or as a PS in aPDT. They also show low cytotoxicity, in vivo biocompatibility, and improved wound healing. Although there are several in vitro and some in vivo investigations describing the nanotechnological aspects and the potential antimicrobial application of CUR-loaded DDSs, clinical trials are not reported and further studies should translate this evidence to the clinical scenarios of infections.

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