Formation of leukotrienes and other hydroxy acids during platelet-neutrophil interactions in vitro

Marcus, Aaron J.; Broekman, M. Johan; Safier, Lenore B.; Ullman, H L; Islam, Naziba; Serhan, Charles N.; Rutherford, L E; Korchak, Helen M.; Weissmann, Gerald

doi:10.1016/0006-291x(82)91575-3

Cited by 292 publications

(81 citation statements)

References 14 publications

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“…In addition to increased LTB4 synthesis, the coincubation of platelets and PMNL resulted in the formation of products derived from metabolic cooperation between the two cell types. Figure 1 shows that activated platelet and PMNL mixtures produced 55,12S-DiHETE, which is a product of the double dioxygenation of arachidonic acid by the 5-and 12-lipoxygenases Marcus et al, 1982). The product of the co-oxidation of the 5S,12S-DiHETE in the PMNL, the 5S,12S,20-TriHETE (Lindgren et al, 1981), was always formed in substantial amounts, while the 12-HETE metabolite, 12,20-DiHETE (Marcus et al, 1984) was also present but in smaller amounts.…”

Section: Discussionmentioning

confidence: 99%

“…LTA4 released by PMNL is metabolized by platelets into LTC4 (Maclouf et al, 1989) and lipoxins (Serhan, 1990). It was also demonstrated that PMNL stimulated with the ionophore A23187 in the presence of platelets transform platelet-derived 12S-hydroxy-5, 8,10,14-(Z,Z,E,Z)-eicosatetraenoic acid (12-HETE) into 5S,12S-dihydroxy-6,8,10,14(E,Z,E,Z)-eicosatetraenoic acid (5S, 12S-DiHETE) Marcus et al, 1982), and arachidonic acid into LTB4 (Marcus et al, 1982) via the 5-lipoxygenase pathway. In addition, 12-HETE synthesized in platelets is metabolized to 12S,8,10,14(Z,Z,E, by unstimulated neutrophils (Marcus et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

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Thrombin‐activated platelets promote leukotriene B₄ synthesis in polymorphonuclear leucocytes stimulated by physiological agonists

Palmantier

Borgeat

1991

British J Pharmacology

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The addition of 2 × 108 human platelets to 8 × 106 polymorphonuclear leucocytes (PMNL) incubated in presence of 2.5 u ml−1 thrombin and 0.1 μm N‐formyl‐Met‐Leu‐Phe (FMLP) (or C5a or PAF) led to enhancement of leukotriene B4 (LTB4) synthesis by the PMNL (measured by h.p.l.c. as 20‐hydroxy‐ and 20‐carboxy‐LTB4) from 4 ± 1 pmol (in absence of platelets) to 26 ± 4 pmol (mean ± s.e.mean, n = 9). Platelets and thrombin were both essential for the enhancement of LTB4 synthesis. Platelets also caused enhancement of LTB4 synthesis from (30 ± 12 to 134 ± 25 pmol, n = 6) when PMNL pretreated with granulocyte‐macrophage colony‐stimulating factor were used in similar experiments. Enhancement of LTB4 synthesis was also observed (from 5 ± 1.5 to 26.5 ± 5 pmol, n = 9) when the supernatants of thrombin‐activated platelet suspensions were added to FMLP‐stimulated PMNL. Supernatants of platelet suspensions activated by thrombin in presence of cyclo‐oxygenase and 12‐lipoxygenase inhibitors led to greater enhancement (from 5 ± 3 to 153.5 ± 27.5 pmol, n = 3) of LTB4 synthesis by FMLP‐stimulated PMNL, suggesting that arachidonic acid itself, rather than its metabolites was responsible for the effects of platelets. Addition of arachidonic acid to FMLP‐stimulated PMNL at a concentration comparable to that measured in thrombin‐activated platelet supernatants (0.2 ± 0.025 μm, n = 6) mimicked the effect of platelets or platelet supernatants on LTB4 synthesis in FMLP‐activated PMNL. The present data indicate that under conditions of cell activation by physiological agonists, platelets can significantly increase the formation of the proinflammatory compound LTB4 in PMNL by providing arachidonic acid. These data lend support to the concept that platelet‐PMNL interactions could modulate the inflammatory process.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thrombin‐activated platelets promote leukotriene B₄ synthesis in polymorphonuclear leucocytes stimulated by physiological agonists

Palmantier

Borgeat

1991

British J Pharmacology

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“…Expanding on this concept, we define thromboregulation as a process or group of processes by which circulating hematologic cells and cells of the vessel wall interact to regulate or inhibit thrombus formation. Essentially, all thromboregulatory reactions are biochemical in nature and result in formation of biologically active metabolites that could have only arisen through interactions between heterogeneous cell types in the vasculature (Marcus et al, 1980(Marcus et al, , 1982(Marcus et al, , 1988Valles et al, 1993Valles et al, , 2002Serhan and Oliw, 2001). Thromboregulation is accomplished by biological compounds that are either cellassociated or released from the cell into the fluid-phase microenvironment.…”

Section: Hemostasis and Thrombosis As Models Of Cell-cell Interactionsmentioning

confidence: 99%

Metabolic Control of Excessive Extracellular Nucleotide Accumulation by CD39/Ecto-Nucleotidase-1: Implications for Ischemic Vascular Diseases

Marcus

Broekman

Drosopoulos

et al. 2003

J Pharmacol Exp Ther

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122

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Platelets are responsible for maintaining vascular integrity. In thrombocytopenic states, vascular permeability and fragility increase, presumably due to the absence of this platelet function. Chemical or physical injury to a blood vessel induces platelet activation and platelet recruitment. This is beneficial for the arrest of bleeding (hemostasis), but when an atherosclerotic plaque is ulcerated or fissured, it becomes an agonist for vascular occlusion (thrombosis). Experiments in the late 1980s cumulatively indicated that endothelial cell CD39 -an ecto-ADPase-reduced platelet reactivity to most agonists, even in the absence of prostacyclin or nitric oxide. As discussed herein, CD39 rapidly and preferentially metabolizes ATP and ADP released from activated platelets to AMP, thereby drastically reducing or even abolishing platelet aggregation and recruitment. Since ADP is the final common agonist for platelet recruitment and thrombus formation, this finding highlights the significance of CD39. A recombinant, soluble form of human CD39, solCD39, has enzymatic and biological properties identical to the full-length form of the molecule and strongly inhibits human platelet aggregation induced by ADP, collagen, arachidonate, or TRAP (thrombin receptor agonist peptide). In sympathetic nerve endings isolated from guinea pig hearts, where neuronal ATP enhances norepinephrine exocytosis, solCD39 markedly attenuated norepinephrine release. This suggests that NTPDase (nucleoside triphosphate diphosphohydrolase) could exert a cardioprotective action by reducing ATP-mediated norepinephrine release, thereby offering a novel therapeutic approach to myocardial ischemia and its consequences. In a murine model of stroke, driven by excessive platelet recruitment, solCD39 reduced the sequelae of stroke, without an increase in intracerebral hemorrhage. CD39 null mice, generated by deletion of apyrase-conserved regions 2 to 4, exhibited a decrease in postischemic perfusion and an increase in cerebral infarct volume when compared with controls. "Reconstitution" of CD39 null mice with solCD39 reversed these changes. We hypothesize that solCD39 has potential as a novel therapeutic agent for thrombotic diatheses. The Hemostatic MechanismThe hemostatic process consists of a series of physiologic and biochemical reactions that culminate in the arrest of bleeding from blood vessels that have been severed or traumatized physically or chemically. Hemostasis is accomplished via the interaction of three biological systems: 1) components of the vasculature per se, including endothelial cells; 2) blood platelets; and 3) plasma proteins comprising the intrinsic and extrinsic coagulation pathways (Marcus, 1999). Qualitative or quantitative deficiencies in any one of these systems result in a defect of hemostasis, coagulation, or both. These abnormalities can lead to a hemorrhagic diathesis that is clinically mild, moderate, or severe. -methyladenosine-3Ј,5Ј-diphosphate; NTPDase, nucleoside triphosphate diphosphohydrolase.

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“…It seemed possible that a 12-lipoxygenase or 15-lipoxygenase product could account for the biological activity known as "endothelial cell derived relaxing factor," EDRF. 35 We have taken two approaches to testing the ability of lipoxygenase products to relax arterial smooth muscle. First, we have tested the biological activity of authentic standards.…”

Section: Involvement In Cell-cell Interactionsmentioning

confidence: 99%

A review of possible roles of the platelet 12-lipoxygenase.

Brash¹

1985

Circulation

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Formation of leukotrienes and other hydroxy acids during platelet-neutrophil interactions in vitro

Cited by 292 publications

References 14 publications

Thrombin‐activated platelets promote leukotriene B₄ synthesis in polymorphonuclear leucocytes stimulated by physiological agonists

Thrombin‐activated platelets promote leukotriene B₄ synthesis in polymorphonuclear leucocytes stimulated by physiological agonists

Metabolic Control of Excessive Extracellular Nucleotide Accumulation by CD39/Ecto-Nucleotidase-1: Implications for Ischemic Vascular Diseases

A review of possible roles of the platelet 12-lipoxygenase.

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Formation of leukotrienes and other hydroxy acids during platelet-neutrophil interactions in vitro

Cited by 292 publications

References 14 publications

Thrombin‐activated platelets promote leukotriene B4 synthesis in polymorphonuclear leucocytes stimulated by physiological agonists

Thrombin‐activated platelets promote leukotriene B4 synthesis in polymorphonuclear leucocytes stimulated by physiological agonists

Metabolic Control of Excessive Extracellular Nucleotide Accumulation by CD39/Ecto-Nucleotidase-1: Implications for Ischemic Vascular Diseases

A review of possible roles of the platelet 12-lipoxygenase.

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Thrombin‐activated platelets promote leukotriene B₄ synthesis in polymorphonuclear leucocytes stimulated by physiological agonists

Thrombin‐activated platelets promote leukotriene B₄ synthesis in polymorphonuclear leucocytes stimulated by physiological agonists