Soluble Factor(s) Released from Neutrophils Activates Endothelial Cell Matrix Metalloproteinase-2

Schwartz, Jess D.; Monea, Sara; Marcus, Stuart G.; Patel, Sundeep; K, Eng; Galloway, Aubrey C.; Mignatti, Paolo; Shamamian, Peter

doi:10.1006/jsre.1998.5294

Cited by 45 publications

(30 citation statements)

References 23 publications

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“…This conformational change either directly activates the MMPs or allows other proteases to activate them, i.e., neutrophil elastase (43,44). HOCl is a much more potent activator of MMP-2, MMP-7, MMP-8, and MMP-9 than H 2 O 2 , its oxidative precursor.…”

Section: Role Of Reactive Oxygen Species In Enhancing Tumor Cell Progmentioning

confidence: 99%

“…Neutrophils produce and release high levels of MMP-9/gelatinase B, but produce little, if any, MMP-2, which plays an important role in the turnover of various ECM components (42). Neutrophils release a soluble factor in response to IL-8, which activates latent MMP-2 released by other cells (43). In response to IL-8, neutrophils, endothelial cells, and lymphocytes release a specific sulfatase and a heparanase, which are instrumental in releasing embedded growth factors from the ECM (27,28).…”

Section: Neutrophils In Remodeling the Extracellular Matrixmentioning

confidence: 99%

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The Potential Role of Neutrophils in Promoting the Metastatic Phenotype of Tumors Releasing Interleukin-8

Larco

Wuertz

Furcht

2004

Clinical Cancer Research

368

268

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In the last decade, several groups have shown a direct correlation between the inappropriate or ectopic release of interleukin (IL)-8 by tumor cells in vitro and their growth and metastatic potential using in vivo models of tumor growth. IL-8 is a potent neutrophil chemoattractant. Neutrophils, as "early responders" to wounds and infections, release enzymes to remodel the extracellular matrix of the tissues through which they migrate to reach the site of the wound or infection. It is proposed that the host's cellular response to IL-8 released by tumor cells enhances angiogenesis and contributes to tumor growth and progression. The activities released by the responding neutrophils could serve as enablers of tumor cell migration through the extracellular matrix, helping them enter the vasculature and journey to new, metastatic sites. The reactive oxygen species produced by neutrophilic oxidases to kill invading organisms have the potential to interact with tumor cells to attenuate their apoptotic cascade and increase their mutational rate. It is proposed that the increase in metastatic potential of tumors ectopically releasing IL-8 is, in part, attributable to their ability to attract neutrophils. Discussed here are possible mechanisms by which the neutrophils responding to ectopic IL-8 contribute to the in vivo growth, progression, and metastatic potential of tumor cells. Possible targets are also presented for the development of therapies to attenuate the effects of the ectopic IL-8 release by tumor cells. DISCOVERY OF INTERLEUKIN-8The cytokine interleukin (IL)-8 is a small basic protein first purified on the basis of its neutrophil chemoattractant properties (1, 2). Soon after it was purified, a cDNA clone was obtained, and its gene was characterized (3, 4). IL-8 is a member of the ␣-chemokine family and a very potent neutrophil chemoattractant. It and its homologs are induced in wounds by the G 0 to G 1 transition, and its expression is greatly enhanced by the inflammatory mediators IL-1␤ and tumor necrosis factor (TNF) ␣ (5, 6). IL-8 recruits neutrophils to the site of wounds to protect the tissue from invading microorganisms and enhance the healing process (7). However, the release of IL-8 by the wrong cells, at the wrong time, or at too high a concentration can lead to undesired pathologies, such as rheumatoid arthritis, inflammatory bowel disease, idiopathic pulmonary fibrosis, and cerebral and myocardial ischemia (8). ECTOPIC INTERLEUKIN-8 EXPRESSIONIn the last decade, several groups have observed a direct correlation between the level of ectopic IL-8 expression by individual clones of tumor cell lines and their in vivo growth rate and metastatic potential. This correlation has been shown for many tumor cell types (9 -13) as well as for fresh breast tumor samples (14). Highly metastatic tumor cells produce more IL-8 constitutively than their poorly metastatic counterparts, and the amounts of IL-8 they release in response to the pro-inflammatory cytokines IL-1␤ and TNF-␣ are much greater (13, 15). ...

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Section: Role Of Reactive Oxygen Species In Enhancing Tumor Cell Progmentioning

confidence: 99%

Section: Neutrophils In Remodeling the Extracellular Matrixmentioning

confidence: 99%

The Potential Role of Neutrophils in Promoting the Metastatic Phenotype of Tumors Releasing Interleukin-8

Larco

Wuertz

Furcht

2004

Clinical Cancer Research

368

268

View full text Add to dashboard Cite

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“…Polymorphonuclear neutrophils (PMNs) are rich in MMP-9 (PMN gelatinase) (36), and PMNderived proteinases activate MMP-2 and MMP-9 in vivo (7) and in cell culture (35). A variety of inflammatory mediators are also involved in vascular remodeling.…”

mentioning

confidence: 99%

Matrix metalloproteinase expression in vein grafts: role of inflammatory mediators and extracellular signal-regulated kinases-1 and -2

Sharony¹,

Pintucci²,

Saunders³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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Mignatti. Matrix metalloproteinase expression in vein grafts: role of inflammatory mediators and extracellular signal-regulated kinases-1 and -2. Am J Physiol Heart Circ Physiol 290: H1651-H1659, 2006. First published November 11, 2005 doi:10.1152/ajpheart.00530.2005.-Matrix metalloproteinases (MMPs) play key roles in vascular remodeling. We characterized the role of inflammatory mediators and extracellular signal-regulated kinases (ERKs) in the control of arterialized vein graft expression of MMP-9, MMP-2, and membrane-type 1-MMP (MT1-MMP) and of the tissue inhibitor of metalloproteinases-2 (TIMP-2). For this purpose we used a canine model of jugular vein to carotid artery interposition graft and analyzed the vein grafts at various postoperative times (30 min to 28 days) using the contralateral vein as a control. To study the role of ERK-1/2, veins were incubated with the mitogen-activated protein kinase kinase (MEK-1/2) inhibitor UO126 for 30 min before being grafted. Vein graft extracts were analyzed for MMPs, TIMP-2, tumor necrosis factor-␣ (TNF-␣), polymorphonuclear neutrophil (PMN) infiltration, myeloperoxidase (MPO), and thrombin activity, and for ERK-1/2 activation. Vein graft arterialization resulted in rapid and sustained (8 h to 28 days) upregulation of vein graft-associated MMP-9, MMP-2, MT1-MMP, thrombin activity, and TNF-␣ levels with concomitant TIMP-2 downregulation. MMP-2 activation preceded MT1-MMP upregulation. PMN infiltration and vein graft-associated MPO activity increased within hours after arterialization, indicating a prompt, local inflammatory response. In cultured smooth muscle cells, both thrombin and TNF-␣ upregulated MT1-MMP expression; however, only thrombin activated MMP-2. Inhibition of ERK-1/2 activation blocked arterializationinduced upregulation of MMP-2, MMP-9, and MT1-MMP. Thus, thrombin, inflammatory mediators, and activation of the ERK-1/2 pathway control MMP and TIMP-2 expression in arterialized vein grafts.inflammation; mitogen-activated protein kinase; vascular remodeling VEIN GRAFT exposure to arterial circulation often results in intimal hyperplasia and medial hypertrophy, with eventual luminal stenosis and reocclusion. The process of vein graft stenosis involves migration and proliferation of smooth muscle cells (SMCs), along with excess deposition of extracellular proteins such as collagen (44).Matrix metalloproteinases (MMPs), a family of zinc-and calcium-dependent proteinases, collectively degrade all protein components of the extracellular matrix (ECM; 21). SMCs and macrophages in atherosclerotic and balloon-injured arteries express increased levels of MMP-9, MMP-2, and membranetype 1 metalloproteinase (MT1-MMP) (30). MMP-2 appears to have particular requirements for activation, entailing interaction with plasma membrane-tethered MMPs (the MT-MMPs) and formation of a trimolecular complex consisting of proMMP-2, MT-MMP, and tissue inhibitor of metalloproteinases-2 (TIMP-2) (38). MT1-MMP-bound MMP-2 is also activated by thrombin (23), plasmin, and neutrophil prote...

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“…Both elastase and plasmin are known inducers of MMP activation. In fact, soluble factors released by neutrophils, particularly elastase, have been shown to activate metalloproteinase-2 (26,27). Elastase was also reported to activate MMP-9 in vivo (28).…”

Section: Discussionmentioning

confidence: 99%

Predominant Role of Host Proteases in Myocardial Damage Associated with Infectious Endocarditis Induced by Enterococcus faecalis in a Rat Model

et al. 2013

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f Infective endocarditis (IE) remains a life-threatening infectious disease with high morbidity and mortality. The objectives of the present study are to assess the host proteolytic activities of the vegetations and their cytotoxic potential in a rat model of experimental IE. Rats were infected with a strain of Enterococcus faecalis of particularly low virulence and weak protease expression. We tested the presence of proteases released by infiltrated leukocytes (matrix metalloproteinases and elastase) or produced in situ within the septic vegetation, such as those linked to the fibrinolytic system (plasmin and plasminogen activators). We also assessed the tissue damage induced by the infective thrombus in vitro and ex vivo. The model of IE was characterized by larger and more extensive vegetations in infected than in nonseptic rats and by an intense neutrophil infiltrate interfacing with the injured underlying tissue. Neutrophil extracellular DNA was shown to trap bacteria and to produce increased levels of cell-free DNA in plasma. Matrix metalloproteinase-9, elastase, and plasminogen activators were increased in septic versus nonseptic vegetations (as shown by zymography and immunohistology). Finally, proteolysis of the extracellular matrix and apoptosis were shown to be associated with host proteases. Bacteria exhibited no detectable proteolytic activity or direct cytotoxic effects. Bacterial membranes/dead bacteria were sufficient to induce leukocyte recruitment and activation that could promote vegetation formation and growth. Our results suggest that, despite the lack of bacterial proteases, the continuous attractant signals coming from bacterial colonies may lead to a chronic and deleterious aggression toward myocardial/valvular tissues by host proteases.

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Soluble Factor(s) Released from Neutrophils Activates Endothelial Cell Matrix Metalloproteinase-2

Cited by 45 publications

References 23 publications

The Potential Role of Neutrophils in Promoting the Metastatic Phenotype of Tumors Releasing Interleukin-8

The Potential Role of Neutrophils in Promoting the Metastatic Phenotype of Tumors Releasing Interleukin-8

Matrix metalloproteinase expression in vein grafts: role of inflammatory mediators and extracellular signal-regulated kinases-1 and -2

Predominant Role of Host Proteases in Myocardial Damage Associated with Infectious Endocarditis Induced by Enterococcus faecalis in a Rat Model

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