Role for Myeloid Nuclear Differentiation Antigen in the Regulation of Neutrophil Apoptosis during Sepsis

Fotouhi‐Ardakani, Nasser; Kebir, Driss El; Pierre-Charles, Natacha; Wang, Lili; Ahern, Stéphane P.; Filep, János G.; Milot, Éric

doi:10.1164/rccm.201001-0075oc

Cited by 44 publications

(60 citation statements)

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“…The latter protein category included the ␣M-␤ 2 integrin complex (CD11b/CD18) and grancalcin (50), myosin-If (51), and the CD177 neutrophil surface marker (52). The myeloid cell nuclear differentiation antigen (MNDA) manipulates neutrophil apoptosis (53). Two previous studies identified neutrophil proteins via proteomics from urethral catheter samples but did not include experiments comparing ASB patients to UTI patients (13,21).…”

Section: Discussionmentioning

confidence: 99%

Similar Neutrophil-Driven Inflammatory and Antibacterial Responses in Elderly Patients with Symptomatic and Asymptomatic Bacteriuria

et al. 2015

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bDifferential diagnosis of asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) is based on the presence of diverse symptoms, including fever (>38.5°C), rigors, malaise, lethargy, flank pain, hematuria, suprapubic discomfort, dysuria, and urgent or frequent urination. There is consensus in the medical community that ASB warrants antibiotic treatment only for patients undergoing urological procedures that lead to mucosal bleeding, catheterized individuals whose ASB persists for more than 48 h after catheter removal, and pregnant women. Pyuria is associated with UTI and implicates host immune responses via release of antibacterial effectors and phagocytosis of pathogens by neutrophils. Such responses are not sufficiently described for ASB. Metaproteomic methods were used here to identify the pathogens and evaluate molecular evidence of distinct immune responses in cases of ASB compared to UTI in elderly patients who were hospitalized upon injury. Neutrophil-driven inflammatory responses to invading bacteria were not discernible in most patients diagnosed with ASB compared to those with UTI. In contrast, proteomic urine analysis for trauma patients with no evidence of bacteriuria, including those who suffered mucosal injuries via urethral catheterization, rarely showed evidence of neutrophil infiltration. The same enzymes contributing to the synthesis of leukotrienes LTB 4 and LTC 4 , mediators of inflammation and pain, were found in the UTI and ASB cohorts. These data support the notion that the pathways mediating inflammation and pain in most elderly patients with ASB are not quantitatively different from those seen in most elderly patients with UTI and warrant larger clinical studies to assess whether a common antibiotic treatment strategy for elderly ASB and UTI patients is justified. U ncomplicated urinary tract infections (UTI) affect the health of approximately 150 million people worldwide and 7 million people in the United States annually; the majority of those affected are women (1). Ascending to the kidneys, UTIs lead to pyelonephritis, which is estimated to have an incidence of 12 cases per 10,000 women in the United States (2). Catheter-associated urinary tract infection (CAUTI), in particular, that seen following long-term catheterization, is characterized by biofilm formation on luminal and external urethral catheter surfaces and frequently causes nosocomial infections. CAUTIs are complicated UTIs because the rate of recurrence is higher and the effectiveness of short-term antibiotic treatment is decreased (3, 4). The incidence of CAUTIs, especially of CAUTIs contracted by elderly patients in long-term care centers and hospitals and by patients with spinal cord injuries and neurogenic bladders (3, 4), is estimated to be 0.9 to 1.5 million cases per year in the United States (1, 3). The infections are deemed potentially preventable complications of hospitalization by the Center of Medicare and Medicaid Services, and the associated costs are no longer reimbursed (3). Escherichia coli causes ...

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Section: Discussionmentioning

confidence: 99%

Similar Neutrophil-Driven Inflammatory and Antibacterial Responses in Elderly Patients with Symptomatic and Asymptomatic Bacteriuria

et al. 2015

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“…Thus during apoptosis, MNDA is cleaved by caspases and then relocalises to the cytosol where it accumulates and associates with the antiapoptotic protein myeloid cell leukaemia 1 (MCL1). This leads to MCL1 degradation, resulting in apoptosis caused by mitochondrial dysfunction [12]. This relocalisation of MNDA to the cytosol is thought to be required for proper execution of apoptosis and suggests that reduced cytoplasmic accumulation of MNDA contributes to suppression of neutrophil apoptosis.…”

Section: Early Research On the Human Pyhinsmentioning

confidence: 99%

“…This relocalisation of MNDA to the cytosol is thought to be required for proper execution of apoptosis and suggests that reduced cytoplasmic accumulation of MNDA contributes to suppression of neutrophil apoptosis. Furthermore, in septic patients cytoplasmic accumulation and cleavage of MNDA in neutrophils was dramatically impaired [12].…”

Section: Early Research On the Human Pyhinsmentioning

confidence: 99%

“…AIM2 and POP3 are predominantly cytosolic proteins, while IFI16, MNDA and PYHIN1 are predominantly found in the nucleus owing to the presence of an N-terminal nuclear localisation sequence (NLS) [3,9]. However, other factors such as acetylation or the presence of stimulatory DNA (in the case of IFI16), or the onset of apoptosis (in the case of MNDA), can also influence their cellular localisation [10][11][12].…”

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The emerging role of human PYHIN proteins in innate immunity: Implications for health and disease

Connolly

Bowie

2014

Biochemical Pharmacology

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“…Delayed apoptotic activity of peripheral blood neutrophils is observed in the course of various diseases, for example, respiratory distress syndrome in adults [25], sepsis [55][56][57][58], bacterial and viral pneumonia [59,60], exacerbation of bronchoectatic disease [61], rheumatoid arthritis [62], cystic fibrosis [63,64] and burns [65]. The correlation between the neutrophil apoptosis level and the disease severity is well established [55,58].…”

Section: Role Of Neutrophil Apoptosis In the Resolution Of Inflammationmentioning

confidence: 99%

The Role of Neutr Ophils and Their Apoptosis in There Solution of Inflammation

Pavlyshyn¹,

Sarapuk²

2015

PU-HSP

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puls Uczelni 2015 (9) 4Niniejszy materiał jest udostępniony na licencji creative commons -Uznanie autorstwa 4.0 pL.Pełne postanowienia tej licencji są dostępne na: http://creativecommons.org/licenses/by-nc-sa/4.0/legalcode Prace poglądowe | Reviews DOI: 10.5604/2081DOI: 10.5604/ -2021 tHe rOLe OF NeUtrOpHiLS AND tHeir ApOptOSiS iN tHe reSOLUtiON OF iNFLAMMAtiONRola granulocytów obojętnochłonnych i ich apoptozy w zwalczaniu stanu zapalnego A -przygotowanie projektu badania | study design, B -zbieranie danych | data collection, C -analiza statystyczna | statistical analysis, D -interpretacja danych | data interpretation, E -przygotowanie maszynopisu | manuscript preparation, F -opracowanie piśmiennictwa | literature search, G -pozyskanie funduszy | funds collection SUMMARY Inflammation, as a part of the body's immune response, is present in the progression of most diseases. Neutrophils form the first line of the defense against invading pathogens and subsequently play a prominent role in the resolution of inflammation.They have a protective function as they release antibacterial enzymes and generate reactive oxygen species. Neutrophils are able to regulate the inflammatory reaction by undergoing apoptosis. Apoptosis, then, facilitates cellular homeostasis ( immune defense), promotes the elimination of activated cells of the immune system, and can act as a major pathogenetic link of an inflammation process, defining its character. This review highlights the mechanisms of apoptosis, the influence of external and internal factors and infectious agents (viruses, extracellular and intracellular microorganisms) on the enactment of neutrophil programmed death and the resolution of inflammation. Keywords: neutrophils, apoptosis, inflammation STRESZCZENIEStan zapalny jako część odpowiedzi immunologicznej organizmu jest patologiczną podstawą większości chorób. Granulocyty obojętnochłonne tworzą pierwszą linię obrony przed inwazją patogenów i odgrywają znaczącą rolę w zwalczaniu stanu zapalnego. Realizują one funkcję ochronną poprzez uwalnianie enzymów przeciwbakteryjnych i wytwarzanie wolnych rodników. Granulocyty obojętnochłonne są w stanie regulować reakcję zapalną poprzez apoptozę. Apoptoza zapewnia homeostazę komórek, ochronę immunologiczną, nasila eliminację aktywowanych komórek układu odpornościowego oraz może stanowić znaczący związek patogenetyczny z procesem zapalnym, określając jego charakter. W artykule zwrócono uwagę na mechanizmy apoptozy, wpływ czynników zewnętrznych i wewnętrznych oraz czynników zakaźnych (wirusy, wewnątrzkomórkowe i zewnątrz-komórkowe mikroorganizmy) na realizację zaprogramowanej śmierci granulocytów obojętnochłonnych i zwalczanie stanu zapalnego.Słowa kluczowe: granulocyty obojętnochłonne, apoptoza, stan zapalny (PU-HSP 2015; 9, 4: 18-25)

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Role for Myeloid Nuclear Differentiation Antigen in the Regulation of Neutrophil Apoptosis during Sepsis

Abstract: These results indicate that cytoplasmic accumulation of MNDA facilitates progression of apoptosis and suggest that impaired cytoplasmic MNDA accumulation contributes to delayed neutrophil apoptosis in patients with severe sepsis.

Cited by 44 publications

References 44 publications

Similar Neutrophil-Driven Inflammatory and Antibacterial Responses in Elderly Patients with Symptomatic and Asymptomatic Bacteriuria

Similar Neutrophil-Driven Inflammatory and Antibacterial Responses in Elderly Patients with Symptomatic and Asymptomatic Bacteriuria

The emerging role of human PYHIN proteins in innate immunity: Implications for health and disease

The Role of Neutr Ophils and Their Apoptosis in There Solution of Inflammation

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