Expression of an endothelial-type nitric oxide synthase isoform in human neutrophils: modification by tumor necrosis factor-alpha and during acute myocardial infarction

Frutos, Trinidad de; Miguel, Lourdes Sánchez de; Farré, Jerónimo; Gómez, Juan; Romero, José R.; Marcos‐Alberca, Pedro; Núñez, Antonio; Rico, Luís; López‐Farré, Antonio

doi:10.1016/s0735-1097(00)01185-2

Cited by 56 publications

(35 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…eNOS is also expressed in both mouse and human neutrophils, monocytes, and macrophages, as well as in human immature myeloid cells (81)(82)(83)(84)(85)(86)(87). In the mouse model, on the other A proposed model for signaling mechanisms of MDL-1-mediated shock.…”

Section: Figurementioning

confidence: 99%

Activation of MDL-1 (CLEC5A) on immature myeloid cells triggers lethal shock in mice

Cheung¹,

Shen²,

Phillips³

et al. 2011

J. Clin. Invest.

View full text Add to dashboard Cite

Systemic inflammatory response syndrome (SIRS) is a potentially lethal condition, as it can progress to shock, multi-organ failure, and death. It can be triggered by infection, tissue damage, or hemorrhage. The role of tissue injury in the progression from SIRS to shock is incompletely understood. Here, we show that treatment of mice with concanavalin A (ConA) to induce liver injury triggered a G-CSF-dependent hepatic infiltration of CD11b + Gr-1 + Ly6G + Ly6C + immature myeloid cells that expressed the orphan receptor myeloid DAP12-associated lectin-1 (MDL-1; also known as CLEC5A). Activation of MDL-1 using dengue virus or an agonist MDL-1-specific antibody in the ConA-treated mice resulted in shock. The MDL-1 + cells were pathogenic, and in vivo depletion of MDL-1 + cells provided protection. Triggering MDL-1 on these cells induced production of NO and TNF-α, which were found to be elevated in the serum of treated mice and required for MDL-1-induced shock. Surprisingly, MDL-1-induced NO and TNF-α production required eNOS but not iNOS. Activation of DAP12, DAP10, Syk, PI3K, and Akt was critical for MDL-1-induced shock. In addition, Akt physically interacted with and activated eNOS. Therefore, triggering of MDL-1 on immature myeloid cells and production of NO and TNF-α may play a critical role in the pathogenesis of shock. Targeting the MDL-1/Syk/PI3K/Akt/eNOS pathway represents a potential new therapeutic strategy to prevent the progression of SIRS to shock.

show abstract

Section: Figurementioning

confidence: 99%

Activation of MDL-1 (CLEC5A) on immature myeloid cells triggers lethal shock in mice

Cheung¹,

Shen²,

Phillips³

et al. 2011

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…However, presence of both nNOS and iNOS has been accepted unequivocally (23)(24)(25), whereas occurrence of eNOS in human neutrophils (26), is still being advocated. Rodents are commonly exploited for the various NO-mediated investigations.…”

mentioning

confidence: 99%

Functional and molecular characterization of NOS isoforms in rat neutrophil precursor cells

et al. 2010

View full text Add to dashboard Cite

Previous studies from this laboratory have demonstrated importance of neutrophilderived nitric oxide (NO) in free radical generation, characterized nitric oxide synthase (NOS) isoforms, and have reported subcellular distribution of NOS in rat peripheral neutrophils. Maximum number of neutrophils are added per day to the circulation from bone marrow, thus neutrophils might add substantial amount of NO in the bone marrow. NO generating ability and NOS isoforms characteristics in bone marrow neutrophil precursor cells is, however, still unexplored. This study was, therefore, undertaken to investigate NO generation ability and the molecular/biochemical characteristics of NOS isoforms in neutrophil precursor cells. The neutrophil precursors were separated on Percoll density gradient and characterized by Giemsa staining, CD markers, and by their size and granularity at various stages of maturation as Bands 1, 2, and 3. Mature neutrophils were efficient in free radical generation and phagocytosis, whereas immature cells had more mitochondria and myeloperoxidase. Amount of NO augmented from immature to mature neutrophils as assessed by fluorescent probe DAF-2DA and Griess reagent. Measurement of NOS enzyme activity further confirmed the functional status of NOS in these cells. NOS isoforms were differentially expressed during neutrophil maturation as confirmed by enzyme activity, Western blotting, flowcytometry, and RT-PCR. Expression of nNOS was predominantly stable in all the stages of neutrophil maturation. iNOS expression was, however, consistently augmented during maturation, whereas eNOS expression was downregulated with neutrophil maturation. Furthermore, all NOS isoforms proteins were distributed in cytosol as well as nucleus as assessed by confocal microscopy. This study for the first time report biochemical and molecular characteristics of NOS isoforms in rat neutrophil precursor cells. ' 2010 International Society for Advancement of Cytometry Key terms nitric oxide; NOS; neutrophils; neutrophil precursor cells; maturation NEUTROPHILS (PMNs) are orchestrating cells of the innate immune system (1,2), circulating through the body and extravasating to the sites of infection and injury, to perform important roles in the host defense. This process involves recruitment of lysosomes and various types of granules to release proteolytic enzymes, antimicrobial peptides, and free radical formation (1,2). PMN development in the bone marrow has classically been divided into six stages myeloblasts (MBs), promyelocytes (PMs), myelocytes (MCs), metamyelocytes (MMs), band cells (BCs), and segmented neutrophil on the basis of cell size, nuclear morphology, and granule content (3,4). Production of these cells is continuous to provide the continual demand for the tissues and mostly to maintain the circulating pool in the blood.Nitric oxide (NO), a versatile signaling molecule, mediates immune response, vasodilation, neurotransmission, proliferation, and apoptosis (5-8). NO is synthesized by a class of NADPH-dependent N...

show abstract

“…In vitro studies have shown that inflammation, and more particularly cytokines are intimately involved in the downregulation of eNOS protein in both the endothelium and leukocytes. 19,20 In this regard, a recent review from Jeremy et al 21 and Giugliano et al 22 have suggested a relationship between ED and inflammation. The expression of eNOS protein seem to be preserved in the mononuclear cells from the patients with ED of neurological origin, which could be related to a lower production of inflammatory mediators than in the patients with ED of vascular origin.…”

Section: Discussionmentioning

confidence: 99%

Soluble guanylate cyclase β1-subunit expression is increased in mononuclear cells from patients with erectile dysfunction

Mateos-Cáceres

García-Cardoso

et al. 2006

Int J Impot Res

View full text Add to dashboard Cite

The aim was to determine in circulating mononuclear cells from patients with erectile dysfunction (ED), the level of expression of endothelial nitric oxide synthase (eNOS), soluble guanylate cyclase (sGC) b 1 -subunit and phosphodiesterase type-V (PDE-V). Peripheral mononuclear cells from nine patients with ED of vascular origin and nine patients with ED of neurological origin were obtained. Fourteen age-matched volunteers with normal erectile function were used as control. Reduction in eNOS protein was observed in the mononuclear cells from patients with ED of vascular origin but not in those from neurological origin. Although sGC b 1 -subunit expression was increased in mononuclear cells from patients with ED, the sGC activity was reduced. However, only the patients with ED of vascular origin showed an increased expression of PDE-V. This work shows for the first time that, independently of the aetiology of ED, the expression of sGC b 1 -subunit was increased in circulating mononuclear cells; however, the expression of both eNOS and PDE-V was only modified in the circulating mononuclear cells from patients with ED of vascular origin.

show abstract

Expression of an endothelial-type nitric oxide synthase isoform in human neutrophils: modification by tumor necrosis factor-alpha and during acute myocardial infarction

Abstract: These observations demonstrate that human neutrophils express eNOS, which is downregulated by TNF-alpha and during AMI. This effect is associated with increased binding of neutrophil cytosolic proteins to the 3'-UTR of eNOS mRNA.

Cited by 56 publications

References 35 publications

Activation of MDL-1 (CLEC5A) on immature myeloid cells triggers lethal shock in mice

Activation of MDL-1 (CLEC5A) on immature myeloid cells triggers lethal shock in mice

Functional and molecular characterization of NOS isoforms in rat neutrophil precursor cells

Soluble guanylate cyclase β1-subunit expression is increased in mononuclear cells from patients with erectile dysfunction

Contact Info

Product

Resources

About