The molecular species composition of individual diacyl phospholipids in human platelets

Mahadevappa, Vhundi G.; Holub, Bruce J.

doi:10.1016/0005-2760(82)90168-0

Cited by 110 publications

(18 citation statements)

References 31 publications

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“…In comparison to mammalian leukocytes, the PE levels of the amebocyte (42.2%) were about 60% greater than those seen in platelets and macrophages (23-29%), whereas PC levels (36.3%) were at the lower end of the range seen in these leukocytes (35-46%) (24)(25)(26). The higher PE levels in the amebocyte may reflect differences in immune response between invertebrate and vertebrate lymphocytes.…”

Section: Discussionmentioning

confidence: 87%

“…Whereas diacyl species dominated in the PE lipid pools of mammalian leukocytes, ether lipids made up almost three-quarters of the amebocyte PE species. The major PE species reported in mammalian leukocytes were 16:0a/20:4, 18:0a/20:4, 16:0a/18:1, and 16:0a/18:2 (21,24,26). The predominant Limulus PE species, 20:1p/20:5 and 20:1p/20:4, were unusual with the eicosene (20:1) group in the sn-1 position.…”

Section: Discussionmentioning

confidence: 98%

“…Within the phospholipid classes, a number of overall similarities existed between the molecular species distribution of PS and PI in the amebocyte with vertebrate platelets and macrophages. In the human platelet, the predominant diacyl molecular species of PS are 18:0a/20:4 (41%) and 18:0a/18:1 (37%) (24), but in the mouse macrophage, PS has three major species 16:0a/18:1 (41.1%), 18:0a/18:1 (19.8%), and 18:0a/20:4 (11.1%) (21). The PS profile of the amebocyte was more similar to the platelet than the macrophage with its predominant PS species of 18:0a/20:4 (34%) and 18:0a/18:1 (23%).…”

Section: Discussionmentioning

confidence: 99%

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Phospholipid composition of the granular amebocyte from the horseshoe crab, Limulus polyphemus

MacPherson

Pavlovich²,

Jacobs

1998

Lipids

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The phospholipid composition was determined for the amebocyte of the primitive arthropod Limulus polyphemus. The total fatty acid composition of the cells' lipids was analyzed by gas chromatography/mass spectrometry (GC/MS) of fatty acid methyl esters (FAME). The FAME analysis revealed high levels of 20-carbon polyunsaturated fatty acids (PUFA), especially arachidonic (20:4n-6) and eicosapentaenoic (20:5n-3) acids. Almost 20% of the total lipid profile was comprised of dimethyl acetals of 16- to 20-carbon chain lengths, indicative of plasmalogens in the phospholipid pool. Phospholipids, analyzed by high-pressure liquid chromatography, included phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylinositol (PI), sphingomyelin (SPH), and cardiolipin (CL). PE and PC levels predominated at 42.2 and 36.3%, respectively. Smaller amounts of PS (9.0%) and PI (6.2%) were present, as well as low levels of SPH (4.6%), CL (1.6%), and trace amounts of lysophosphatidylcholine. The major phospholipid species, PE, PC, PS and PI, were collected and their molecular species were examined by electrospray-ionization mass spectrometry. The molecular species within the phospholipid classes reflected the high levels of PUFA seen in the total lipid profile. PI was mainly composed of 18:0a/20:4. Over half of the PS consisted of 18:0a/18:1 and 18:0a/20:4. The major PE species were 20:1p/20:5, 20:1p/20:4, 18:0p/20:5, and 18:0p/20:4. PC had the largest distribution of molecular species, and its most abundant species were 16:0e/20:5, 16:0e/20:4, and 16:0p/20:4. The presence of 16:0e/20:4 is the first documentation of a specific precursor to platelet-activating factor in an invertebrate hemocyte. Note: at the sn-1 position: [a=1=O-acyl, e = 1-O-alkylether, and p = 1-O-alk-1'-enyl (plasmalogen)].

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Phospholipid composition of the granular amebocyte from the horseshoe crab, Limulus polyphemus

MacPherson

Pavlovich²,

Jacobs

1998

Lipids

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“…Arachidonate and linoleate are almost exclusively located in the sn2 position of platelet and plasma phospholipids (35,36). Thus unsaturated LPAs are generated through the action of PLA 1 enzymes.…”

Section: Figmentioning

confidence: 99%

Multiple Mechanisms Linked to Platelet Activation Result in Lysophosphatidic Acid and Sphingosine 1-Phosphate Generation in Blood

Sano¹,

Baker²,

Virág³

et al. 2002

Journal of Biological Chemistry

243

239

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Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (Sph1P) production was examined in vitro under conditions that simulated blood clotting. Several approaches were utilized to elucidate the metabolic pathways. 1) Platelet phospholipids were labeled using [ 32 P]orthophosphate, and the production of [ 32 P]Sph1P and LPA was examined. Thrombin stimulation of platelets resulted in rapid secretion of Sph1P stored within the platelet. In contrast, LPA was neither stored within nor secreted from platelets. Nonetheless, extracellular levels of LPA gradually increased following stimulation. 2) Stable-isotope dilution mass spectrometry was used to quantify the molecular species of LPA generated from platelets in vitro. Only 10% of the LPA generated following thrombin stimulation was associated with platelets, the remaining 90% was contained within the extracellular medium. The acyl composition of LPA produced by platelets differed depending on the presence or absence of plasma in the incubation. 3) The fate of exogenously added fluorescent phospholipid analogs was determined. Incubation of [(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]dodecanoyl-(NBD)-labeled phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine with the supernatant fractions from thrombin-stimulated platelets yielded no LPA production. However, these lipids were converted to the corresponding lysolipids by released PLA 1 and PLA 2 activities. When incubated with plasma or serum the NBD-labeled lysophospholipids were readily converted to LPA. Inhibitors of lysophospholipase D and the biological activity of LPA were detected in plasma. These results suggest that the bulk of LPA produced through platelet activation results from the sequential cleavage of phospholipids to lysophospholipids by released phospholipases A 1 and A 2 and then to LPA by plasma lysophospholipase D.Lysophosphatidic acid (LPA) 1 and sphingosine 1-phosphate (Sph1P) are phospholipid mediators with pleiotropic growth factor properties that elicit their actions via the activation of G protein-coupled receptors encoded by the endothelial differentiation gene family (1, 2). Several investigators have identified platelets as the source of Sph1P and LPA. However, contradictions exist in the literature concerning the mechanisms by which these mediators are generated. Although some investigators found no Sph1P generation in thrombin-activated platelets (3), others reported as much as 0.5 M Sph1P in human serum (4). Although it is generally agreed that LPA is generated in thrombin-activated platelets (3, 5, 6), the rate of production found at 0.02 nmol/min/10 9 platelet cannot account for the 5-10 M concentration detected in human serum (7). During the first hour of blood clotting the concentration of LPA increases ϳ300 nM; however, its production continues and an additional 5 M is added to serum during the first 24 h, a time course that is hard to reconcile with that of platelet activation and consequently of platelet only origin. Gerrard and Robinson (6) quantified the molecul...

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“…The known phospholipid composition of the human platelet membrane (22) indicates high heterogeneity considering both of these factors. The platelet membranes are dominated by the zwitterionic phosphatidylcholine, sphingomyelin, and phosphatidylethanolamine (83 mol % of total phospholipid) with a significant fraction of anionic phosphatidylserine and phosphatidylinositol (17 mol %).…”

mentioning

confidence: 99%

Phospholipid Barrier to Fibrinolysis

Váradi¹,

Kolev²,

Tenekedjiev³

et al. 2004

Journal of Biological Chemistry

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The massive presence of phospholipids is demonstrated in frozen sections of human arterial thrombi. Purified platelet phospholipids and synthetic phospholipids retard in vitro tissue-type plasminogen activator (tPA)-induced fibrinolysis through effects on plasminogen activation and plasmin function. The inhibition of plasminogen activation on the surface of fibrin correlates with the fraction of anionic phospholipid. The phospholipids decrease the amount of tPA penetrating into the clot by 75% and the depth of the reactive surface layer occupied by the activator by up to 30%, whereas for plasmin both of these parameters decrease by ϳ50%. The phospholipids are not only a diffusion barrier, they also bind the components of the fibrinolytic system. Isothermal titration calorimetry shows binding characterized with dissociation constants in the range 0.35-7.64 M for plasmin and tPA (lower values with more negative phospholipids). The interactions are endothermic and thermodynamically driven by an increase in entropy, probably caused by the rearrangements in the ordered gel structure of the phospholipids (in line with the stronger inhibition at gel phase temperatures compared with liquid crystalline phase temperatures). These findings show a phospholipid barrier, which should be overcome during lysis of arterial thrombi.The basis of the current thrombolytic therapy in acute myocardial infarction or ischemic stroke is the administration of plasminogen activators (e.g. tPA 1 and its recombinant variants), which convert the plasminogen in blood plasma or on the surface of the thrombi to plasmin and the latter dissolves fibrin, the solid matrix of thrombi (1). However, persistent recanalization of the occluded blood vessels often fails (in 15-40% of patients), and efficient doses of thrombolytics have significant bleeding side effects (2). The limitations of existing fibrinolytic therapy indicate that thrombolysis is not identical to fibrinolysis and direct attention to the variety of cellular and molecular factors present in thrombi that modulate the function of the basal fibrinolytic machinery (recently reviewed in Ref.3).Platelets render thrombi resistant to lysis with tPA (4), which can be partially explained by their PAI-1 content (5), but evidence for PAI-1-independent inhibition of fibrinolysis also exists (6). When arterial thrombi are formed, the platelet content of 10 ml of whole blood is compacted in a volume of 400 l, whereas the fibrin content of the same thrombi corresponds to the fibrinogen concentration in blood plasma (7), the intrathrombus plasminogen (0.4 M), and ␣ 2 -PI (0.25 M) concentrations are just fractions of the respective plasma values (8). After activation, the platelets release their cytosolic content and lose the majority of their phospholipid (9). By taking into account the average amount of phospholipids in platelets (10), the phospholipid content of arterial thrombi (7.5 g/liter) is expected to be higher than their fibrin content (1.7 g/liter). Phospholipids are known to bind fibrinogen a...

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The molecular species composition of individual diacyl phospholipids in human platelets

Cited by 110 publications

References 31 publications

Phospholipid composition of the granular amebocyte from the horseshoe crab, Limulus polyphemus

Phospholipid composition of the granular amebocyte from the horseshoe crab, Limulus polyphemus

Multiple Mechanisms Linked to Platelet Activation Result in Lysophosphatidic Acid and Sphingosine 1-Phosphate Generation in Blood

Phospholipid Barrier to Fibrinolysis

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