Neutrophil Recruitment to the Lungs during Bacterial Pneumonia

Craig, Ann; John, D.; Cai, Shanshan; Jeyaseelan, Samithamby

doi:10.1128/iai.00832-08

Cited by 291 publications

(331 citation statements)

References 95 publications

Supporting

Mentioning

323

Contrasting

Unclassified

Order By: Relevance

“…LPS-induced acute lung injury is marked by increased neutrophil influx and up-regulation of proinflammatory cytokines. Similar phenotypes are observed in other lung inflammatory conditions, including asthma (6), chronic obstructive pulmonary disease (7), and pneumonia (8,9). LPS-mediated lung inflammation is associated with breast and colon cancer metastasis to the lungs (10)(11)(12).…”

mentioning

confidence: 51%

Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1

Rayes

Catena

Lee

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

180

147

View full text Add to dashboard Cite

Inflammation is inextricably associated with primary tumor progression. However, the contribution of inflammation to tumor outgrowth in metastatic organs has remained underexplored. Here, we show that extrinsic inflammation in the lungs leads to the recruitment of bone marrow-derived neutrophils, which degranulate azurophilic granules to release the Ser proteases, elastase and cathepsin G, resulting in the proteolytic destruction of the antitumorigenic factor thrombospondin-1 (Tsp-1). Genetic ablation of these neutrophil proteases protected Tsp-1 from degradation and suppressed lung metastasis. These results provide mechanistic insights into the contribution of inflammatory neutrophils to metastasis and highlight the unique neutrophil protease-Tsp-1 axis as a potential antimetastatic therapeutic target.T he contribution of inflammation to primary tumor progression is well documented (1); however, little is known about its role in metastatic outgrowth in distant organs. The lung, which is a frequent site of metastasis from extrapulmonary neoplasms, is susceptible to inflammatory insults. Bacterial infection-induced, metastasis-conducive environments in the lung (2, 3) and cigarette smoke-induced inflammation were associated with pulmonary metastasis from breast cancer (2, 4).Bacterial lipopolysaccharide (LPS) is a well-characterized inducer of inflammation because its binding to toll-like receptor 4 (TLR4) results in nuclear factor kappa B (NF-κB) activation and expression of proinflammatory cytokines, including interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and IL-6 (5). LPS-induced acute lung injury is marked by increased neutrophil influx and up-regulation of proinflammatory cytokines. Similar phenotypes are observed in other lung inflammatory conditions, including asthma (6), chronic obstructive pulmonary disease (7), and pneumonia (8, 9). LPS-mediated lung inflammation is associated with breast and colon cancer metastasis to the lungs (10-12).The mechanisms by which inflammation contributes to metastatic outgrowth in distant organs have remained underexplored. From a clinical perspective, although blocking primary tumor invasion and blocking dissemination are considered effective approaches in suppressing metastasis, an important question is how best to treat patients whose tumor has already metastasized. Thus, approaches are required to block tumor outgrowth in secondary organs for effective treatment of metastatic cancers. In this study, using two independent models of lung inflammation, we show enhanced recruitment of neutrophils, which degranulate to release the Ser proteases, neutrophil elastase (NE) and cathepsin G (CG), to degrade thrombospondin-1 (Tsp-1) in the lung microenvironment, enhancing metastatic outgrowth. Protease deficiency protected Tsp-1 from proteolysis and suppressed metastasis, providing a previously unidentified mechanism of Tsp-1 regulation in the metastatic organ. Results Neutrophil-Mediated Lung Inflammation Enhances MetastaticOutgrowth. To determine the contribu...

show abstract

mentioning

confidence: 51%

Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1

Rayes

Catena

Lee

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

180

147

View full text Add to dashboard Cite

show abstract

“…Pneumococcal pneumonia causes abundant neutrophil infiltration (13). The innate immune system in humans provokes acute inflammation at the onset of infection, but at the same time, neutrophil activation massively contributes to inflammatory tissue damage (14).…”

mentioning

confidence: 99%

α-Enolase of Streptococcus pneumoniae Induces Formation of Neutrophil Extracellular Traps

Mori

Yamaguchi

Terao

et al. 2012

Journal of Biological Chemistry

104

View full text Add to dashboard Cite

“…This is demonstrated in patients with HIV and AIDS. The reduction of neutrophil recruitment in disease models stimulated by bacteria often results in decreased bacterial clearance and reduced survival (Craig et al, 2009). This also occurs in patients suffering from leukocyte adhesion deficiency, a disease characterized by a defect in leukocyte extravasation.…”

Section: Discussionmentioning

confidence: 99%

Distribution of CXCR2 +1208 T/C gene polymorphisms in relation to opportunistic infections among HIV-infected patients in Limpopo Province, South Africa

Samie¹,

Dzhivhuho²,

Nangammbi³

2014

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. Interleukin 8 (IL-8) is a chemokine produced by macrophages and other cell types, including epithelial cells, and its receptor is CXCR2. IL-8 plays an important role in the initiation and amplification of inflammatory diseases, including opportunistic infections. With the advent of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome, opportunistic infections have become major health concerns. However, the role of host genetics on the occurrence of these infections has not been clearly defined. In this study, genomic DNA was extracted from 185 HIVinfected individuals in the Limpopo Province, South Africa. Allelespecific polymerase chain reaction was used to genotype the CXCR2 +1208 T/C gene. Genotypes CC, TT, and TC were associated with chest pains, frequent headaches, loss of weight, diarrhea, and loss of appetite among HIV patients. A significant association between the CC CXCR2 gene polymorphism among HIV patients genotype and chest pains was found (P = 0.035). The TC genotype was associated with loss of appetite (P = 0.044) and chest pains (P = 0.042). A weak association between diarrhea and the TT genotype was found (P = 0.082). No association was observed between tuberculosis and the genotypes. Immunological characteristics, such as viral load and CD4 count, were not significantly associated with the genotypes. The results of the present study suggest that carriers of the TC genotype are more susceptible to chest pain, but that this genotype confers a protective effect against loss of appetite. The CC genotype was found to confer protection against chest pain but appeared to increase susceptibility to headaches. Further studies using larger samples are necessary to confirm these results.

show abstract

Neutrophil Recruitment to the Lungs during Bacterial Pneumonia

Cited by 291 publications

References 95 publications

Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1

Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1

α-Enolase of Streptococcus pneumoniae Induces Formation of Neutrophil Extracellular Traps

Distribution of CXCR2 +1208 T/C gene polymorphisms in relation to opportunistic infections among HIV-infected patients in Limpopo Province, South Africa

Contact Info

Product

Resources

About