The Balancing Act of Neutrophils

Bardoel, Bart W.; Kenny, Elaine F.; Sollberger, Gabriel; Zychlinsky, Arturo

doi:10.1016/j.chom.2014.04.011

Cited by 195 publications

(222 citation statements)

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“…Os neutrófilos são células que compõem o sistema imune inato, desempenhando um papel essencial em processos inflamatórios agudos e na defesa do organismo contra patógenos (Kumar;Sharma, 2010;Mantovani et al, 2011;Bardoel et al, 2014).…”

Section: Aspectos Geraisunclassified

“…Além de atuar diretamente na destruição dos patógenos, os neutrófilos também são capazes de produzir mediadores pró-inflamatórios (que contribuem para o recrutamento de novas células para o foco inflamatório), de atuar como células apresentadoras de antígenos e de sinalizar e instruir outras células do sistema imunológico (tais como células dendríticas, macrófagos, células "natural killer", células B e células T), o que evidencia seu importante papel na regulação da resposta imune inata e adaptativa (Abdallah et al, 2011;Mantovani et al, 2011;Bardoel et al, 2014). Adicionalmente, os neutrófilos auxiliam na remoção de células mortas, de corpos celulares gerados por apoptose e de outros "debris" celulares;…”

Section: Aspectos Geraisunclassified

“…além de produzirem citocinas que auxiliam na resolução da inflamação, na cicatrização e na remodelação de tecidos danificados (Borregaard et al, 2007;Kolaczkowska;Kubes, 2013 (Bardoel et al, 2014). Além do núcleo multi-lobulado (com 3 a 5 lóbulos), os neutrófilos apresentam formato esférico com cerca de 12 a 15 µm de diâmetro, e grânulos em abundância no citoplasma.…”

Section: Aspectos Geraisunclassified

“…Quando maduros, os neutrófilos desenvolvem as vesículas secretoras, que são altamente mobilizáveis e contêm, na superfície de suas membranas, componentes enzimáticos, receptores, proteínas sinalizadoras e moléculas de adesão, além de proteínas plasmáticas presentes na matriz (Borregaard et al, 2007;Bardoel et al, 2014).…”

Section: Aspectos Geraisunclassified

“…A fusão dos grânulos com a membrana plasmática ou com a membrana dos fagossomas e a liberação das substâncias microbicidas podem causar a morte dos patógenos. Tais substâncias microbicidas são, principalmente, proteínas e enzimas antimicrobianas como a defensina e a lisozima (que funcionam rompendo a superfície aniônica bacteriana) e proteases (que degradam proteínas bacterianas) (Mayer-Scholl et al, 2004;Pham, 2006;Bardoel et al, 2014). (Faurschou;Borregaard, 2003;Mayer-Scholl et al, 2004;Klüter et al, 2014).…”

Section: -O Processo De Desgranulaçãounclassified

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O extrato etanólico das folhas de Baccharis dracunculifolia (Asteraceae) modula funções efetoras de neutrófilos: um promissor agente fitoterápico para o tratamento de processos inflamatórios mediados por estas células

Rinhel¹

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RibeirãoNeutrophils are phagocytic immune cells mobilized primarily to fight against infections. These cells are capable to kill microorganisms through degranulation, which leads to the release of antimicrobial molecules, and production of reactive oxygen species. Although neutrophil recruitment is essential for host protection, excessive activation of these cells culminates in intense discharge of cytotoxic molecules to the extracellular milieu, which can elicit the development of and/or aggravate the clinical condition in autoimmune and inflammatory diseases such as rheumatoid arthritis. Modulation of the effector functions of neutrophils is a possible therapeutic approach to treat these diseases. Previous studies have shown that the ethanolic extract of Baccharis dracunculifolia leaves (EEBd) has a great therapeutic potential due to its significant antioxidant effect towards the oxidative metabolism of neutrophils. To continue investigating the anti-inflammatory and/or immunomodulatory action of such extract, the first part of the present work examined its modulator effect on three important effector functions of human neutrophils that mediate recognition and clearance of pathogens -phagocytosis, degranulation, and microbial killing -and on the activity of lysosomal enzymes. EEBd inhibited the oxidative metabolism of neutrophils without affecting their defense ability, depending on the extract concentration used. To propose possible chemical markers for the biological effects of the extract, the second part of this study evaluated the antioxidant activity of seven compounds isolated from EEBd -caffeic acid, coumaric acid, ferulic acid, cinnamic acid, aromadendrin-4'-methyl ether, isosakuranetin, and hispidulin -towards the oxidative metabolism of neutrophils. The results pointed to caffeic acid as a potential chemical marker for this biological activity. The third part of this investigation aimed to improve the bioavailability and favor the therapeutic use of the natural products studied. EEBd and caffeic acid were incorporated into liposomal carrier systems. The incorporation of both samples into liposomes did not alter their antioxidant activity towards neutrophils, as compared with their respective free forms. Finally, this study examined the therapeutic effect of EEBd and caffeic acid, both in the free form and incorporated into liposomes, in an animal model of arthritis. The free samples markedly improved the joint inflammatory parameters: they reduced edema and migration of total cells and neutrophils, and slightly lowered the levels of the inflammatory cytokines tumor necrosis factor  and interleukin 6 and 1 (TNF-, IL-6, and IL-1, respectively). In addition, incorporation of EEBd and caffeic acid into liposomes can help to reduce their concentrations required to achieve the desired therapeutic effect. Based on the set of results obtained in this study, we conclude that EEBd has a great potential to become a therapeutic adjuvant in the treatment of neutrophil-mediated inflammatory diseases, and that...

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Section: Aspectos Geraisunclassified

Section: -O Processo De Desgranulaçãounclassified

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O extrato etanólico das folhas de Baccharis dracunculifolia (Asteraceae) modula funções efetoras de neutrófilos: um promissor agente fitoterápico para o tratamento de processos inflamatórios mediados por estas células

Rinhel¹

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Rab32‐related antimicrobial pathway is involved in the progression of dextran sodium sulfate‐induced colitis

Xie

Zhou

et al. 2018

FEBS Open Bio

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Inflammatory bowel disease ( IBD ) is a multifactorial disease involving defective immune responses against invasive microbiota. Genes associated with innate immune responses to microbes have been highlighted in the pathogenesis of IBD . To determine the role of Rab32 in the pathogenesis of IBD , we administered dextran sodium sulfate ( DSS ) to CD 11c + cell‐specific Rab32 knockout ( CD 11c ‐Cre + Rab32 f/f ) mice to induce colitis. Rab32 deficiency in CD 11c + cells resulted in more severe disease progression and increased mortality. Histopathological analysis showed extensive damage to the colon mucosa in DSS ‐treated CD 11c ‐Cre + Rab32 f/f mice, including more severe damage to the epithelial layer and crypts, as well as more inflammatory cell infiltration. The pro‐inflammatory cytokines IL 1A, IL 1B, IL 6, and CSF 3 and chemokines CXCL 1 and CXCL 2 were significantly increased, and the frequency of CD 11b + Ly6G + neutrophils was higher in CD 11c ‐Cre + Rab32 f/f colitis mice. Furthermore, CD 11c + cells deficient for Rab32 exhibited a significant increase in bacterial translocation in inflamed colon tissue. The present data demonstrate that Rab32 knockout in CD 11c + cells aggravates the development of DSS ‐induced colitis and suggest that the Rab32‐related antimicrobial pathway is involved in the pathogenesis of IBD .

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Combating Implant Infections: Shifting Focus from Bacteria to Host

et al. 2020

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commensal skin bacteria, Staphylococci, and in particular Staphylococcus aureus, have a strong tendency to colonize foreign bodies and cause IAI. [3,4] Important for the underlying pathophysiology, Staphylococci are highly competent at producing biofilms on implant surfaces, which encapsulate the bacterial niche from the outside environment, [5,6] thereby protecting the bacteria from host defense systems and antibiotics. [7] Antibiotics are administered as a routine procedure. [8] However, as a consequence of widespread antibiotics usage, bacteria are exposed to subinhibitory concentrations of antibiotics at a larger scale, driving their development toward antibiotic resistance, [9] as illustrated by the emergence of methicillin-resistant S. aureus (MRSA). [10,11] As an improvement over current clinically applied local antibiotics delivery systems, [12] the recent developments in implant surface engineering approaches allow better antimicrobial functionalities to be incorporated to allow for more tunable and controlled drug release. [13-15] The "race to the surface" model is popular among biomaterials researchers to predict the biomaterials fate, resulting from the competition between eukaryotic cells and bacteria at the material surface. [16] Using this template, implant antibacterial properties are being stemmed from direct contact killing mechanisms due to implant surface modifications [17,18] or firm immobilization of drugs, [19,20] as they both "shield" the implant from bacterial adhesion. The current anti-infective biomaterials strategies being explored can be categorized as: 1) implant functionalization with antibiotics or antibacterial drugs such as host defense peptides (HDPs), inorganic materials (e.g., chitosan and derivatives), and inorganics (e.g., silver, copper, and zinc metal nanoparticles (NPs)), 2) anti-biofilm surface modification (e.g., coating with antifouling polymers or quorum sensor inhibitors), or 3) physical surface changes for direct contact-killing properties (e.g., nanotubes, nanopillars, and metal implantation). [15,21] Emerging as a serious alternative or adjuvant therapy to antibiotics, bacteriophage (phage) therapy uses viruses responsible for the lysis of specific bacterial strains. [22,23] As a natural predator of bacteria, phages employ different killing mechanisms, making multidrug resistant bacteria susceptible for phages. [24] Moreover, phages are highly specific for pathogenic cells, which can eliminate disastrous off-target effects in the host. [25] As a limitation, the use of phage cocktails is needed for therapeutic efficacy, [26] while there is currently is no conclusive data on possible long-term side effects of phage therapy in The widespread use of biomaterials to support or replace body parts is increasingly threatened by the risk of implant-associated infections. In the quest for finding novel anti-infective biomaterials, there generally has been a one-sided focus on biomaterials with direct antibacterial properties, which leads to excessive use of antibacterial ag...

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The Balancing Act of Neutrophils

Cited by 195 publications

References 89 publications

O extrato etanólico das folhas de Baccharis dracunculifolia (Asteraceae) modula funções efetoras de neutrófilos: um promissor agente fitoterápico para o tratamento de processos inflamatórios mediados por estas células

O extrato etanólico das folhas de Baccharis dracunculifolia (Asteraceae) modula funções efetoras de neutrófilos: um promissor agente fitoterápico para o tratamento de processos inflamatórios mediados por estas células

Rab32‐related antimicrobial pathway is involved in the progression of dextran sodium sulfate‐induced colitis

Combating Implant Infections: Shifting Focus from Bacteria to Host

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