Tissue injury in neutrophilic inflammation

Dallegri, Franco; Ottonello, Luciano

doi:10.1007/s000110050208

Cited by 185 publications

(159 citation statements)

References 103 publications

Supporting

Mentioning

149

Contrasting

Unclassified

Order By: Relevance

“…Because tumors typically have very poorly developed blood vessels and have regions of hypoxia, 24 small areas of necrosis may arise and produce chemotactic factors for neutrophils, which can in turn generate IL-8. 32 Our IL-8 experiments using MN-11 tumors suggest that an influx of neutrophils is associated with necrosis. Thus, both events can occur: necrosis may recruit neutrophils and neutrophils may produce additional chemoattractants.…”

Section: Discussionmentioning

confidence: 80%

“…For example, interleukin-8 (IL-8), a potent chemoattractant for neutrophils of the C-X-C type, 32 has been shown in glioblastoma. 33 IL-8 has also been identified in human gastric, colorectal and bronchioloalveolar carcinomas 34 -36 and in B-cell chronic lymphocytic leukemia.…”

Section: (Am J Pathol 2000 156:509 -518)mentioning

confidence: 99%

“…38 Recruited neutrophils and hypoxic vascular endothelial cells may be another source of IL-8 and other chemotaxins. 32,39 Since thrombotic occlusion of blood vessels is common in tumors, clottingrelated factors can also contribute to the recruitment of inflammatory cells. 38 Activated platelets can secrete chemokines such as monocyte chemoattractant protein-1 and IL-8.…”

Section: (Am J Pathol 2000 156:509 -518)mentioning

confidence: 99%

See 2 more Smart Citations

Neutrophils, Nitric Oxide Synthase, and Mutations in the Mutatect Murine Tumor Model

Sandhu

Privora

Wenckebach

et al. 2000

The American Journal of Pathology

View full text Add to dashboard Cite

Mutatect MN-11 is a tumor line that can be grown subcutaneously in syngeneic C57BL/6 mice. The frequency of spontaneously arising mutants at the hypoxanthine phosphoribosyltransferase (Hprt) locus was observed to be elevated as a result of in vivo growth. The objective of the present study was to identify factors in the tumor microenvironment that might explain this increase in mutant frequency (MF). When tumors were examined histologically, neutrophils were found to be the predominant infiltrating cell type. Quantitative estimates of the number of neutrophils and MF of tumors in different animals revealed a statistically significant correlation (r ‫؍‬ 0.63, P < 0.0001). Immunohistochemical analysis for inducible nitric oxide synthase (iNOS) demonstrated its presence, mainly in neutrophils. Biochemical analysis of tumor homogenates for nitric oxide synthase (NOS) activity indicated a statistically significant correlation with MF (r ‫؍‬ 0.77, P < 0.0001). Nitrotyrosine was detected throughout the tumor immunohistochemically; both cytoplasmic and nuclear staining was seen. To increase the number of infiltrating neutrophils, tumors were injected with chemoattractant interleukin-8 and prostaglandin E2. This produced a statistically significant increase in neutrophil content (P ‫؍‬ 0.005) and MF (P ‫؍‬ 0.0002). As in control MN-11 tumors, neutrophil content and MF were strongly correlated (r ‫؍‬ 0.63, P ‫؍‬ 0.003). Because neutrophils are a potential source of genotoxic reactive oxygen and/or nitrogen species, our results support the notion that these tumor-infiltrating cells may be mutagenic and contribute to the burden of genetic abnormalities associated with tumor progression.

show abstract

Section: Discussionmentioning

confidence: 80%

Section: (Am J Pathol 2000 156:509 -518)mentioning

confidence: 99%

Section: (Am J Pathol 2000 156:509 -518)mentioning

confidence: 99%

See 1 more Smart Citation

Neutrophils, Nitric Oxide Synthase, and Mutations in the Mutatect Murine Tumor Model

Sandhu

Privora

Wenckebach

et al. 2000

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Neutrophils in the airways undergoing necrosis in situ are a major source of DNA, which makes CF sputum so tenacious [5]. The excessive accumulation of activated neutrophils in the lungs can lead to lung damage [6]. Proinflammatory chemoattractants have been found to be elevated in bronchoalveolar lavage fluid (BAL) from CF, including IL-8, IL-1, IL-6 and tumour necrosis factor alpha (TNFa) [7], leukotriene B 4 (LTB 4 ), complement factors, such as C5a, and bacterial products also act as potent chemoattractants for neutrophils [2].…”

Section: Introductionmentioning

confidence: 99%

Effect of cystic fibrosis exacerbations on neutrophil function

Brockbank

Downey

Elborn

et al. 2005

International Immunopharmacology

View full text Add to dashboard Cite

In cystic fibrosis (CF), inflammation is caused by persistent bacterial infection from Pseudomonas aeruginosa and Burkholderia cenocepacia in the lung and is characterised by the persistent infiltration of massive numbers of neutrophils which leads to lung injury. The aim of this present study was to investigate the effects of CF exacerbations on the reactivity of peripheral blood neutrophils compared to data from a normal healthy control population. Peripheral blood neutrophils were isolated from control subjects and CF patients before and after an exacerbation of their lung disease. Isolated neutrophils were stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol 12-myristate 13-acetate (PMA) and the rate of superoxide generation and elastase activity measured and compared with neutrophils from healthy age-matched controls. Neutrophils from CF patients spontaneously generated higher levels of superoxide after resolution of the exacerbation compared to control neutrophils. The stimulated generation of superoxide from control neutrophils was not significantly different from neutrophils isolated from CF patients either before or after resolution of the CF exacerbation. Neutrophils from CF patients spontaneously released more elastase than control neutrophils but released less elastase than control neutrophils in response to fMLP. The stimulated release of elastase from neutrophils was not significantly different before compared to after resolution of the exacerbation. Neutrophils from CF patients displayed a different pattern of response than those from control subjects; however, CF exacerbations did not appear to modulate neutrophil function. D

show abstract

“…Neutrophil elastase (NE) is a major secretory product from activated neutrophils and is a major contributor to tissue destruction in inflammatory diseases such as acute respiratory distress syndrome (ARDS), lung emphysema, and rheumatoid arthritis 7,8) . It has been reported that α 1 -protease inhibitor (α 1 -PI), an endogenous NE inhibitor, is inactivated by neutrophil -derived reactive oxygen species (ROS) 9) , resulting in attenuation of the NE inhibitory activity of α 1 -PI and a consequent increase in NE activity.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Elastase Inhibitor Suppresses Il-17 Based Inflammation of Murine Experimental Colitis

Shioya

Katakura

Ohira

2014

FJMS

View full text Add to dashboard Cite

: [Background] Neutrophil elastase (NE) is a proteinase in granulocytes and plays an important role in the pathogenesis of inflammatory disorders. It has been reported that NE activity is elevated in both colonic mucosa and blood in inflammatory bowel disease (IBD) patients, and that it can act as an aggravating factor in IBD. To develop novel therapies for IBD, we examined the effects of an NE inhibitor, Elaspor ® , on murine experimental colitis.[Methods] Acute colitis was induced in BALB/c mice by administration of dextran sulfate sodium (DSS) in drinking water for 7 days. NE inhibitor was administered subcutaneously to mice prior to and during the induction of colitis. Disease activity index (DAI), colonic myeloperoxidase (MPO) activity, luminal NE activity, and mRNA expression in the colon were then investigated.[Results] Subcutaneous administration of NE inhibitor ameliorated the severity of DSS -induced colitis. NE activity was elevated in inflamed colon, and was reduced by NE inhibitor administration. mRNA expression levels of IL -17, a Th17 -based inflammatory factor, was also decreased in the colon of NE inhibitor -administered mice.[Conclusion] These results suggest that NE inhibitor ameliorated colonic inflammation by decreasing both the activity of NE and the effects of cytokine balance. Clinically, NE inhibitor improves injuries associated with systemic inflammatory response syndrome. Similarly, clinical use of this inhibitor would further clarify its usefulness in clinical colonic inflammation.

show abstract

Tissue injury in neutrophilic inflammation

Cited by 185 publications

References 103 publications

Neutrophils, Nitric Oxide Synthase, and Mutations in the Mutatect Murine Tumor Model

Neutrophils, Nitric Oxide Synthase, and Mutations in the Mutatect Murine Tumor Model

Effect of cystic fibrosis exacerbations on neutrophil function

Neutrophil Elastase Inhibitor Suppresses Il-17 Based Inflammation of Murine Experimental Colitis

Contact Info

Product

Resources

About