Platelet activation by fMLP-stimulated polymorphonuclear leukocytes: the activity of cathepsin G is not prevented by antiproteinases

Evangelista, Virgilio; Rajtar, G; Gaetano, Giovanni de; Jg, White; Cerletti, Chiara

doi:10.1182/blood.v77.11.2379.2379

Cited by 97 publications

(55 citation statements)

References 34 publications

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“…On activation of whole blood with collagen, the circulating microvesicles were observed to adhere to the neutrophils and monocytes and disruption of the platelet-neutrophil adhesions diminished the intravascular TF activity. Adhesion of platelets to neutrophils has been proposed to result in the formation of a restricted microenvironment, with high local concentrations of the neutrophil secretion products (28). Although the reactive oxygen species are needed to activate the intravascular TF, they apparently act in concert with the neutrophil proteases, which, in parallel, might inactivate tissue factor pathway inhibitor (14).…”

Section: Discussionmentioning

confidence: 99%

Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets

Müller¹,

Klocke²,

Alex³

et al. 2003

FASEB j.

364

275

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Although tissue factor (TF), the principial initiator of physiological coagulation and pathological thrombosis, has recently been proposed to be present in human blood, the functional significance and location of the intravascular TF is unknown. In the plasma portion of blood, we found TF to be mainly associated with circulating microvesicles. By cell sorting with the specific marker CD42b, platelet-derived microvesicles were identified as a major location of the plasma TF. This was confirmed by the presence of full-length TF in microvesicles acutely shedded from the activated platelets. TF was observed to be stored in the α-granules and the open canalicular system of resting platelets and to be exposed on the cell surface after platelet activation. Functional competence of the blood-based TF was enabled when the microvesicles and platelets adhered to neutrophils, as mediated by P-selectin and neutrophil counterreceptor (PSGL-1, CD18 integrins) interactions. Moreover, neutrophil-secreted oxygen radical species supported the intravascular TF activity. The pools of platelet and microvesicle TF contributed additively and to a comparable extent to the overall blood TF activity, indicating a substantial participation of the microvesicle TF. Our results introduce a new concept of TF-mediated coagulation crucially dependent on TF associated with microvesicles and activated platelets, which principally enables the entire coagulation system to proceed on a restricted cell surface.Key words: lipopolysaccharide • platelet rich plasma • superoxide dismutase • catalase • microparticles T wo principal events that are initiated after disrupture of the endothelial barrier are thought to mark the initiation of hemostasis. Blood platelets adhere to subendothelial collagen providing a provisional, mechanically unstable closure of the vessel perforation. Concomitantly, the coagulation process is started. This is mainly due to the formation of an initiator complex between tissue factor (TF), an integral cell membrane protein predominantly present in the adventitial layer of the vessel wall, and the blood-based factor VII/VIIa (1). The TF/factor VIIa complex proteolytically activates factor X, which, in turn, elicits the formation of thrombin. The TF/factor VIIa complex is likely to play a central role in the genesis of arterial and venous thrombosis (2, 3), leading causes of mortality in many countries. TF is present in the lipid rich core of unstable atherosclerotic plaques and may be a major determinant of the thrombogenicity of the plaques (4-6). Indeed, on rupture of the plaque, the interaction of TF with factor VIIa substantially contributes to the rapid formation of the occluding thrombus, the principal final step in the genesis of coronary ischemic disease.Apart from its presence in the vascular wall, TF has also been detected in the blood (intravascular TF). So far, no clear conclusion has been reached about the localization and the functional meaning of the blood-based TF. In the plasma compartment, TF is present un...

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Section: Discussionmentioning

confidence: 99%

Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets

Müller¹,

Klocke²,

Alex³

et al. 2003

FASEB j.

364

275

View full text Add to dashboard Cite

show abstract

“…NSPs reach high concentrations when released into these shielded compartments. At the same time these compartments decrease the access of high-molecularweight inhibitors, such as a1-AT and ACT, respectively (132)(133)(134)(135)(136)(137)(138). The resulting imbalance favors NSP enzymatic activity.…”

Section: Nsps In the Context Of Their Natural Inhibitorsmentioning

confidence: 99%

Neutral serine proteases of neutrophils

Kettritz

2016

Immunological Reviews

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Neutrophil serine proteases (NSPs) exercise tissue-degrading and microbial-killing effects. The spectrum of NSP-mediated functions grows continuously, not least because of methodological progress. Sensitive and specific FRET substrates were developed to study the proteolytic activity of each NSP member. Advanced biochemical methods are beginning to characterize common and specific NSP substrates. The resulting novel information indicates that NSPs contribute not only to genuine inflammatory neutrophil functions but also to autoimmunity, metabolic conditions, and cancer. Tight regulatory mechanisms control the proteolytic potential of NSPs. However, not all NSP functions depend on their enzymatic activity. Proteinase-3 (PR3) is somewhat unique among the NSPs for PR3 functions as an autoantigen. Patients with small-vessel vasculitis develop autoantibodies to PR3 that bind their target antigens on the neutrophil surface and trigger neutrophil activation. These activated cells subsequently contribute to vascular necrosis with life-threatening multiorgan failure. This article discusses various aspects of NSP biology and highlights translational aspects with strong clinical implications.

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“…Although neutrophils adhere poorly to endothelial cells without stimulation of either cell type, stimulation by chemotactic factors induces a marked increase in adhesion which is demonstrable within minutes. Neutrophils may also adhere to each 277 other, causing aggregates that can promote plugging of the microvasculature [12][13][14]. Such aggregation is inhibited by anti-CD18 or anti-CDllb monoclonal antibodies.…”

Section: Increase Of Expression Of Phago-cyte Integrins In Cadmentioning

confidence: 99%

“…Such aggregation is inhibited by anti-CD18 or anti-CDllb monoclonal antibodies. Chemotactic factors are able to induce up-regulation of CD11b/CD18, adhesion receptors include C5a complement factor, cytokines such as interleukin-8 and TNF-a and the lipid mediator platelet activating factor [5,6,13,14]. Recent data suggest that all these agents are potentially released into the coronary circulation of patients with unstable angina.…”

Section: Increase Of Expression Of Phago-cyte Integrins In Cadmentioning

confidence: 99%

“…Interaction of neutrophils with ELAM-1 bearing endothelial cells causes neutrophiis to express enhanced adhesive activity of the integrins CDllb/CD18 [12]. Finally, leukocyte-derived products [12][13][14] enhance platelet aggregation, while products of platelet activation, such as serotonin ADP and platelet-derived growth factor, increase neutrophils' adhesion to endothelial ceils. Therefore, in unstable angina, activated leukocytes and platelets potentiate each other, favouring the occurrence of coronary vasoconstriction and thrombosis.…”

Section: Increase Of Expression Of Phago-cyte Integrins In Cadmentioning

confidence: 99%

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Phagocyte activation in coronary artery disease

Ricevuti¹

1992

FEMS Microbiology Letters

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Recent studies suggest that granulocytes (PMNs) play a role in the pathogenesis of acute and chronic myocardial ischemia and extension of myocardial injury. Granulocytes can release a variety of molecules mediating tissue injury which act synergistically with other molecules and cells. The aim of our investigation was to evaluate the granulocyte function in patients affected by coronary artery disease (CAD) and during coronary angioplasty (PTCA). We studied 20 patients suffering from CAD. The PMN's aggregating activity was greater in the coronary sinus than in the aorta (P<0.01). The increase in aggregating activity was evident in patients who were smokers: their cells release significantly lower quantities of leukotriene C4 (P<0.025). In the 20 patients who underwent coronary angioplasty we analyzed superoxide release after stimulation with phorbolmyristate‐acetate (PMA). The results showed a greater decrease of PMN's superoxide production in the coronary sinus than in the aorta (P<0.05). In all patients affected by CAD we evaluated the PMN's expression of CD11b/CD18 membrane integrins. In these patients the increase in expression of CD11b/CD18 was statistically significant in comparison with the controls (P<0.01). This increase in expression correlates with a higher aggregation (r=0.87, P<0.001). The potential role of leukocytes, oxygen radicals, leukotrienes and granulocyte enzymes in the pathophysiology of myocardial injury due to regional ischemia and reperfusion is an area of intense investigation. This paper presents studies carried out in vivo which have been instrumental in demonstrating the role of granulocytes as mediators of myocardial ischemia.

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Platelet activation by fMLP-stimulated polymorphonuclear leukocytes: the activity of cathepsin G is not prevented by antiproteinases

Cited by 97 publications

References 34 publications

Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets

Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets

Neutral serine proteases of neutrophils

Phagocyte activation in coronary artery disease

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