Unstimulated neutrophils inhibited activation and recruitment of thrombin- or collagen-stimulated platelets in an agonist-specific manner. This occurred under conditions of close physical cell-cell contact, although biochemical adhesion between the cells as mediated by P-selectin was not required. Moreover, in the presence of monoclonal P-selectin antibodies that blocked biochemical platelet-neutrophil adhesion, thrombin-stimulated platelets were more efficiently downregulated by neutrophils. This suggested a prothrombotic role for P-selectin under these circumstances. The neutrophil downregulatory effect on thrombin-stimulated platelets was amplified by lipoxygenase inhibition with 5,8,11,14-eicosatetraynoic acid. In contrast, the neutrophil inhibitory effect on platelets was markedly reduced by platelet-derived 12S-hydroxy-5,8-cis, 10-trans, 14-cis-eicosatetraenoic acid (12S-HETE), as well as by the platelet-neutrophil transcellular product, 12S,20-dihydroxy-5,8,10,14-eicosatetraenoic acid (12S,20-DiHETE), but not by another comparable metabolite, 5S,12S-dihydroxy-6-trans, 8-cis, 10-trans, 14-cis-eicosatetraenoic acid (5S,12S-DiHETE), or the neutrophil-derived hydroxy acid leukotriene B4. The neutrophil downregulatory effect on thrombin-induced platelet reactivity was enhanced by aspirin treatment. This may represent a novel action of aspirin as an inhibitor of platelet function. These results provide in vitro biochemical and functional evidence for the thromboregulatory role of neutrophils and emphasize the multicellular aspect of hemostasis and thrombosis.
J Valles, M T Santos, A J Marcus, L B Safier, M J Broekman, N Islam, H L Ullman, J Aznar
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Role of Human 15-Lipoxygenase-2 in the Biosynthesis of the Lipoxin Intermediate, 5S,15S-diHpETE, Implicated with the Altered Positional Specificity of Human 15-Lipoxygenase-1
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Biochemistry | 2020 |
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Thrombosis Research | 2017 |
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Evaluation of platelet function using multiple electrode platelet aggregometry in dogs with septic peritonitis: Platelet function in septic peritonitis
RH Li, DL Chan |
Journal of Veterinary Emergency and Critical Care | 2016 |
The effects of serum leptin levels on thrombocyte aggregation in peritoneal dialysis patients
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Pakistan Journal of Medical Sciences | 2016 |
Platelets in Inflammation: Regulation of Leukocyte Activities and Vascular Repair
Aà Gros, Và Ollivier, Bà Ho-Tin-Noé |
Frontiers in immunology | 2015 |
Serine/threonine phosphatases regulate platelet αIIbβ3 integrin receptor outside-in signaling mechanisms and clot retraction
A Moscardó, MT Santos, A Latorre, I Madrid, J Vallés |
Life Sciences | 2013 |
Cathepsin G-Dependent Modulation of Platelet Thrombus Formation In Vivo by Blood Neutrophils
N Faraday, K Schunke, S Saleem, J Fu, B Wang, J Zhang, C Morrell, S Dore, A Zarbock |
PloS one | 2013 |
The Influence of Low Platelet Count on Whole Blood Aggregometry Assessed by Multiplate
T Stissing, NP Dridi, SR Ostrowski, L Bochsen, PI Johansson |
Clinical and Applied Thrombosis/Hemostasis | 2011 |
Dangerous connections: neutrophils and the phagocytic clearance of activated platelets
AA Manfredi, P Rovere-Querini, N Maugeri |
Current Opinion in Hematology | 2010 |
The effect of menstrual cycle on platelet aggregation in reproductive-age women
N Melamed, Y Yogev, T Bouganim, E Altman, A Calatzis, M Glezerman |
Platelets | 2010 |
Monocytes downregulate the early stage of collagen-induced platelet activation by a PECAM-1-dependent mechanism
V Ollivier, B Arnaud, M Jandrot-Perrus, N Ajzenberg |
Journal of Thrombosis and Haemostasis | 2009 |
Neutrophils phagocytose activated platelets in vivo: a phosphatidylserine, P-selectin, and 2 integrin-dependent cell clearance program
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Blood | 2009 |
Variables influencing Multiplate™ whole blood impedance platelet aggregometry and turbidimetric platelet aggregation in healthy individuals
UT Seyfert, H Haubelt, A Vogt, P Hellstern |
Platelets | 2007 |
Regulation of cytosolic PlA 2 activity by PP1/PP2A serine/threonine phosphatases in human platelets
A Moscardó, J Vallés, M Piñón, J Aznar, V Martínez-Sales, MT Santos |
Platelets | 2006 |
Aspirin therapy for inhibition of platelet reactivity in the presence of erythrocytes in patients with vascular disease
MT Santos, J Vallés, J Aznar, A Lago, E Sanchez, J Cosin, A Moscardó, M Piñón, MJ Broekman, AJ Marcus |
The Journal of laboratory and clinical medicine | 2006 |
Cytoplasmic free calcium mobilization in platelets, expression of P-selectin, phosphatidylserine, and microparticle formation, measured by whole blood flow cytometry, in hypertensive patients. Effect of doxazosin GITS
M Labiós, M Martínez, F Gabriel, V Guiral, S Ruiz-Aja, J Aznar |
Thrombosis Research | 2006 |
Thrombin and Cardiopulmonary Bypass – A Paradigm for Evaluation of the Regulation of Hemostasis
VA Ferraris, SP Ferraris |
International Journal of Angiology | 2005 |
Leukocyte count and leukocyte ecto-nucleotidase are major determinants of the effects of adenosine triphosphate and adenosine diphosphate on platelet aggregation in human blood
JR Glenn, AE White, A Johnson, SC Fox, MW Behan, G Dolan, S Heptinstall |
Platelets | 2005 |
Metabolic Control of Excessive Extracellular Nucleotide Accumulation by CD39/Ecto-Nucleotidase-1: Implications for Ischemic Vascular Diseases
AJ Marcus, MJ Broekman, JH Drosopoulos, N Islam, DJ Pinsky, C Sesti, R Levi |
The Journal of pharmacology and experimental therapeutics | 2003 |
DDAVP enhances the ability of blood monocytes to form rosettes with activated platelets by increasing the expression of P-selectin sialylated ligands on the monocyte surface
A Pereira, MV Onorato, C Sanz |
British Journal of Haematology | 2003 |
Heterologous cell-cell interactions: thromboregulation, cerebroprotection and cardioprotection by CD39 (NTPDase-1)
AJ Marcus, MJ Broekman, JH Drosopoulos, N Islam, DJ Pinsky, C Sesti, R Levi |
Journal of Thrombosis and Haemostasis | 2003 |
α1-Acid glycoprotein: an acute phase protein with inflammatory and immunomodulating properties
T Hochepied, FG Berger, H Baumann, C Libert |
Cytokine & Growth Factor Reviews | 2003 |
Platelet-erythrocyte interactions enhance αIIbβ3 integrin receptor activation and P-selectin expression during platelet recruitment: down-regulation by aspirin ex vivo
J Vallés, MT Santos, J Aznar, M Martı́nez, A Moscardó, M Piñón, MJ Broekman, AJ Marcus |
Blood | 2002 |
Leukocytes Can Enhance Platelet-mediated Aggregation and Thromboxane Release via Interaction of P-selectin Glycoprotein Ligand 1 with P-selectin
N Faraday, RB Scharpf, JM Dodd-o, EA Martinez, BA Rosenfeld, T Dorman |
Anesthesiology | 2001 |
Maturation Phenomenon in Cerebral Ischemia IV
NG Bazan, U Ito, VL Marcheselli, T Kuroiwa, I Klatzo |
2001 | |
Platelets
JN George |
The Lancet | 2000 |
Heparin, Platelet Aggregation, Neutrophils, and Cardiopulmonary Bypass
PR Belcher, EW Muriithi, EM Milne, P Wanikiat, DJ Wheatley, RA Armstrong |
Thrombosis Research | 2000 |
Hemoglobin stimulates the release of proinflammatory cytokines from leukocytes in whole blood
SJ McFaul, PD Bowman, VM Villa |
Journal of Laboratory and Clinical Medicine | 2000 |
Participation of Tyrosine Phosphorylation in Cytoskeletal Reorganization, α IIb β 3 Integrin Receptor Activation, and Aspirin-Insensitive Mechanisms of Thrombin-Stimulated Human Platelets
MT Santos, A Moscardó, J Vallés, M Martínez, M Piñón, J Aznar, MJ Broekman, AJ Marcus |
Circulation | 2000 |
P-Selectin–Dependent Inhibition of Thrombosis During Venous Stasis
MJ Eppihimer, RG Schaub |
Arteriosclerosis, thrombosis, and vascular biology | 2000 |
The differential effects of aspirin on platelets, leucocytes and vascular endothelium in an in vivo model of thrombus formation
Y Nagamatsu, Y Tsujioka, M Hashimoto, JC Giddings, J Yamamoto |
Clinical and Laboratory Haematology | 1999 |
Targeted inhibition of intrinsic coagulation limits cerebral injury in stroke without increasing intracerebral hemorrhage
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Journal of Experimental Medicine | 1999 |
Reduced microvascular thrombosis and improved outcome in acute murine stroke by inhibiting GP IIb/IIIa receptor-mediated platelet aggregation
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Journal of Clinical Investigation | 1998 |
The effect of aspirin on thrombin stimulated platelet adhesion receptor expression and the role of neutrophils
ML Taylor, MK Ilton, NL Misso, DN Watkins, J Hung, PJ Thompson |
British Journal of Clinical Pharmacology | 1998 |
Increased platelet sensitivity to ADP in mice lacking platelet-type 12-lipoxygenase
EN Johnson, LF Brass, CD Funk |
Proceedings of the National Academy of Sciences | 1998 |
The Platelet Thrombin Receptor and Postoperative Bleeding
VA PhD, SP PhD, A Singh, WF MD, DK MD, D McKenna, ER MD, HR MD |
The Annals of Thoracic Surgery | 1998 |
Platelet-leukocyte interactions
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American Heart Journal | 1998 |
Daily 50 mg or 500 mg Aspirin Does Not Affect the Cooperation of Arachidonic Acid and ADP on Platelet Aggregation
R Altman, A Scazziota, J Rouvier |
Circulation | 1998 |
Erythrocyte Promotion of Platelet Reactivity Decreases the Effectiveness of Aspirin as an Antithrombotic Therapeutic Modality: The Effect of Low-Dose Aspirin Is Less Than Optimal in Patients With Vascular Disease Due to Prothrombotic Effects of Erythrocytes on Platelet Reactivity
J Valles, MT Santos, J Aznar, A Osa, A Lago, J Cosin, E Sanchez, MJ Broekman, AJ Marcus |
Circulation | 1998 |
Nitric oxide released from activated platelets inhibits platelet recruitment
JE Freedman, J Loscalzo, MR Barnard, C Alpert, JF Keaney, AD Michelson |
Journal of Clinical Investigation | 1997 |
Preferential Esterification of Endogenously Formed 5-Hydroxyeicosatetraenoic Acid to Phospholipids in Activated Polymorphonuclear Leukocytes
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European Journal of Biochemistry | 1997 |
Advances in Molecular and Cell Biology
KJ Clemetson |
Advances in Molecular and Cell Biology | 1997 |
Modulation of Platelet Aggregation Response by Factors Released from Polymorphonuclear Leukocytes
M Dikshit, R Kumari |
Hematology | 1997 |
Prothrombotic Effects of Erythrocytes on Platelet Reactivity: Reduction by Aspirin
MT Santos, J Valles, J Aznar, AJ Marcus, MJ Broekman, LB Safier |
Circulation | 1997 |
Simply Read: Erythrocytes Modulate Platelet Function: Should We Rethink the Way We Give Aspirin?
B Rocca, GA FitzGerald |
Circulation | 1997 |
Blockade of C5a and C5b-9 generation inhibits leukocyte and platelet activation during extracorporeal circulation
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Changing concepts in investigations of haemostasis
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Clinical & Laboratory Haematology | 1995 |
Effects of Aspirin on Platelet-Neutrophil Interactions: Role of Nitric Oxide and Endothelin-1
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Circulation | 1995 |
12-Lipoxygenases and 12(S)-HETE: role in cancer metastasis
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Cancer and Metastasis Reviews | 1994 |