scholarly journals Influence of new antimicrobial peptides of the medicinal leech Hirudo medicinalis on the functional activity of neutrophil granule proteins

2021 ◽  
Vol 21 (3) ◽  
pp. 49-62
Author(s):  
Daria V. Grigorieva ◽  
Irina V. Gorudko ◽  
Ekaterina N. Grafskaia ◽  
Ivan A. Latsis ◽  
Alexey V. Sokolov ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Peroxidase Activity ◽  
Functional Activity ◽  
Neutrophil Elastase ◽  
Medicinal Leech ◽  
Hirudo Medicinalis ◽  
Specific Substrate ◽  
Elastase Activity ◽  
Promising Alternative ◽  
Halogenative Stress

BACKGROUND: Resistance of microorganisms caused dangerous to human health infections to traditional antibiotics is a serious problem for healthcare. In this regard, the development of new effective antimicrobial drugs and therapeutic approaches is an urgent task. Antimicrobial peptides (AMPs) are considered a promising alternative to traditional antibiotic in the fight against resistant microorganisms. AIM: The aim of this work is to study the effect of new synthesized AMPs of the medicinal leech Hirudo medicinalis (including under conditions of development of oxidative/halogenative stress) on the functional activity of neutrophils granular proteins the main effector cells of the immune system. MATERIALS AND METHODS: Myeloperoxidase peroxidase activity was assessed by the rate of o-dianisidine oxidation. Neutrophil elastase activity was determined by the fluorescence method using a specific substrate MeOSuc-AAPV-AMC. Lactoferrin iron-binding activity was assessed spectrophotometrically by the change in absorption of protein solution after addition of Fe3+ salt. Lysozyme activity was determined by the rate of M. lysodeikticus bacterial cells lysis. RESULTS: Native AMPs 536_1 and 19347_2 inhibited and 12530 increased myeloperoxidase peroxidase activity, this tendency persisted after these AMPs modification by hypochlorous acid (HOCl). In contrast to the native AMP halogenated AMP 3967_1 acquired the ability to enhance myeloperoxidase enzymatic activity. In the presence of AMP 3967_1 neutrophil elastase amidolytic activity increased insignificantly, while AMP 19347_2 inhibited neutrophil elastase activity. After HOCl modification these AMPs retained their ability to regulate neutrophil elastase activity. Synergistic effects (~20%) against gram-positive bacteria M. lysodeikticus were revealed for combination of lysozyme with AMPs 12530 and 3967_1. Inhibition lysozyme antimicrobial activity was observed in the presence of AMPs 19347_2 and 536_1, however the severity of this effect decreased after AMPs modification by HOCl. After HOCl modification AMP 3967_1 increased, while AMP 12530 on the contrary acquired the ability to inhibit lysozyme mucolytic activity. CONCLUSIONS: The use of drugs based on studied AMPs of medicinal leech will have a beneficial effect on the bodys fight against infectious agents due to the antimicrobial action of AMPs themselves. But in addition studied AMPs are capable to modulate the biological activity of own endogenous antimicrobial proteins and peptides: to enhance it, if it is necessary to eliminate pathogen and to inhibit if it necessary to protect against damage to the bodys own tissues.

scholarly journals Aedes aegypti (Diptera: Culicidae) Immune Responses with Different Feeding Regimes Following Infection by the Entomopathogenic Fungus Metarhizium anisopliae

Insects ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 95 ◽  
Author(s):  
Sara Cabral ◽  
Adriano de Paula ◽  
Richard Samuels ◽  
Rodrigo da Fonseca ◽  
Simone Gomes ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Immune Responses ◽  
Antimicrobial Peptides ◽  
Fungal Infection ◽  
Fat Body ◽  
Negative Regulator ◽  
Toll Pathway ◽  
Promising Alternative ◽  
Imd Pathway ◽  
Feeding Regimes

The mosquito Aedes aegypti is the most notorious vector of illness-causing viruses. The use of entomopathogenic fungi as bioinsecticides is a promising alternative for the development of novel mosquito control strategies. We investigate whether differences in immune responses could be responsible for modifications in survival rates of insects following different feeding regimes. Sucrose and blood-fed adult A. aegypti females were sprayed with M. anisopliae 1 × 106 conidia mL−1, and after 48 h, the midgut and fat body were dissected. We used RT-qPCR to monitor the expression of Cactus and REL1 (Toll pathway), IMD, REL2, and Caspar (IMD pathway), STAT and PIAS (JAK-STAT pathway), as well as the expression of antimicrobial peptides (Defensin A, Attacin and Cecropin G). REL1 and REL2 expression in both the midgut and fat body were higher in blood-fed fungus-challenged A. aegypti than in sucrose-fed counterparts. Interestingly, infection of sucrose-fed insects induced Cactus expression in the fat body, a negative regulator of the Toll pathway. The IMD gene was upregulated in the fat body in response to fungal infection after a blood meal. Additionally, we observed the induction of antimicrobial peptides in the blood-fed fungus-challenged insects. This study suggests that blood-fed A. aegypti are less susceptible to fungal infection due to the rapid induction of Toll and IMD immune pathways.

scholarly journals WS02.2 Role of soluble and membrane-associated neutrophil elastase activity in cystic fibrosis sputum

2017 ◽  
Vol 16 ◽  
pp. S3
Author(s):  
A.S. Dittrich ◽  
I. Kühbandner ◽  
S. Gehrig ◽  
V. Rickert-Zacharias ◽  
C.C. Taggart ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Neutrophil Elastase ◽  
Elastase Activity ◽  
Cystic Fibrosis Sputum

scholarly journals Up-regulation of Neurohemerythrin Expression in the Central Nervous System of the Medicinal Leech,Hirudo medicinalis, following Septic Injury

2004 ◽  
Vol 279 (42) ◽  
pp. 43828-43837 ◽  
Author(s):  
David Vergote ◽  
Pierre-Eric Sautière ◽  
Franck Vandenbulcke ◽  
Didier Vieau ◽  
Guillaume Mitta ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Medicinal Leech ◽  
Hirudo Medicinalis ◽  
The Central Nervous System

Microglia of medicinal leech (Hirudo medicinalis) express a specific activation marker homologous to vertebrate ionized calcium-binding adapter molecule 1 (Iba1/alias aif-1)

2014 ◽  
Vol 74 (10) ◽  
pp. 987-1001 ◽  
Author(s):  
Francesco Drago ◽  
Pierre-Eric Sautière ◽  
Françoise Le Marrec-Croq ◽  
Alice Accorsi ◽  
Christelle Van Camp ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Medicinal Leech ◽  
Hirudo Medicinalis ◽  
Ionized Calcium ◽  
Activation Marker ◽  
Adapter Molecule

scholarly journals A point-of-care neutrophil elastase activity assay identifies bronchiectasis severity, airway infection and risk of exacerbation

2019 ◽  
Vol 53 (6) ◽  
pp. 1900303 ◽  
Author(s):  
Amelia Shoemark ◽  
Erin Cant ◽  
Luis Carreto ◽  
Alexandria Smith ◽  
Martina Oriano ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Point Of Care ◽  
Severity Index ◽  
Forced Expiratory Volume ◽  
Lateral Flow ◽  
Elastase Activity ◽  
Lateral Flow Device ◽  
Airway Infection ◽  
Independent Validation ◽  
Flow Device

IntroductionNeutrophil elastase activity in sputum can identify patients at high risk of airway infection and exacerbations in bronchiectasis. Application of this biomarker in clinical practice is limited, because no point-of-care test is available. We tested whether a novel semi-quantitative lateral flow device (neutrophil elastase airway test stick – NEATstik®) can stratify bronchiectasis patients according to severity, airway infection and exacerbation risk.MethodsSputum samples from 124 patients with stable bronchiectasis enrolled in the UK and Spain were tested using the NEATstik®, which scores neutrophil elastase concentration from 0 (<8 µg·mL−1 elastase activity) to 10 (maximum detectable neutrophil elastase activity). High neutrophil elastase activity was regarded as a NEATstik® grade >6. Severity of disease, airway infection from sputum culture and exacerbations over the 12 months were recorded. An independent validation was conducted in 50 patients from Milan, Italy.Measurements and main resultsPatients had a median age of 69 years and forced expiratory volume in 1 s (FEV1) 69%. High neutrophil elastase activity was associated with worse bronchiectasis severity using the bronchiectasis severity index (p=0.0007) and FEV1 (p=0.02). A high NEATstik® grade was associated with a significant increase in exacerbation frequency, incident rate ratio 2.75 (95% CI 1.63–4.64, p<0.001). The median time to next exacerbation for patients with a NEATstik® grade >6 was 103 days compared to 278 days. The hazard ratio was 2.59 (95% CI 1.71–3.94, p<0.001). Results were confirmed in the independent validation cohort.ConclusionsA novel lateral flow device provides assessment of neutrophil elastase activity from sputum in minutes and identifies patients at increasing risk of airway infection and future exacerbations.

Monocyte inflammation augments acrolein-induced Muc5ac expression in mouse lung

1999 ◽  
Vol 277 (3) ◽  
pp. L489-L497 ◽  
Author(s):  
Michael T. Borchers ◽  
Scott Wesselkamper ◽  
Susan E. Wert ◽  
Steven D. Shapiro ◽  
George D. Leikauf
Keyword(s):  
Gene Expression ◽  
Neutrophil Elastase ◽  
Airway Hyperreactivity ◽  
Mouse Lung ◽  
Mrna Levels ◽  
Elastase Activity ◽  
Mucus Hypersecretion ◽  
Mucin Gene ◽  
Cell Counts ◽  
Macrophage Accumulation

Acrolein, an unsaturated aldehyde found in smog and tobacco smoke, can induce airway hyperreactivity, inflammation, and mucus hypersecretion. To determine whether changes in steady-state mucin gene expression ( Muc2 and Muc5ac) are associated with inflammatory cell accumulation and neutrophil elastase activity, FVB/N mice were exposed to acrolein (3.0 parts/million; 6 h/day, 5 days/wk for 3 wk). The levels of Muc2 and Muc5ac mRNA were determined by RT-PCR, and the presence of Muc5ac protein was detected by immunohistochemistry. Total and differential cell counts were determined from bronchoalveolar lavage (BAL) fluid, and neutrophil elastase activity was measured in the BAL fluid supernatant. Lung Muc5ac mRNA was increased on days 12and 19, and Muc5ac protein was detected in mucous granules and on the surface of the epithelium on day 19. Lung Muc2 mRNA was not detected at measurable levels in either control or exposed mice. Acrolein exposure caused a significant and persistent increase in macrophages and a rapid but transient increase in neutrophils in BAL fluid. Recoverable neutrophil elastase activity was not significantly altered at any time after acrolein exposure. To further examine the role of macrophage accumulation in mucin gene expression, additional strains of mice (including a strain genetically deficient in macrophage metalloelastase) were exposed to acrolein for 3 wk, and Muc5ac mRNA levels and macrophage accumulation were measured. The magnitude of macrophage accumulation coincided with increased Muc5ac mRNA levels, indicating that excessive macrophage accumulation augments acrolein-induced Muc5ac synthesis and secretion after repeated exposure. These findings support a role for chronic monocytic inflammation in the pathogenesis of mucus hypersecretion observed in chronic bronchitis.

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