An essential role for lysophosphatidylcholine in the inhibition of platelet aggregation by secretory phospholipase A2

    Research output: Contribution to journalArticleResearchpeer-review

    46 Citations (Scopus)

    Abstract

    The release of secretory phospholipase A2 (sPLA2) into the mammalian circulation may contribute to the development of hemorrhagic and inflammatory diseases. sPLA2 has previously been shown to alter the behavior of platelets, leukocytes, and endothelial cells, although the molecular basis for these cellular effects has not been established. Our studies indicate that the inhibition of platelet aggregation by snake, bee venom, and pancreatic sPLA2 is dependent on a plasma cofactor. This cofactor resides within the lipoprotein fraction of plasma, with 54%, 31%, and 11% of the activity present in the high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low density lipoprotein (VLDL) fractions, respectively. Delipidation of HDL and LDL was associated with the complete loss of platelet-inhibitory activity. Incubation of purified sPLA2 with the HDL fraction of plasma resulted in the time-dependent generation of lysophosphatidylcholine (lysoPC). The formation of lysoPC correlated with the inhibition of platelet aggregation. Purified lysoPC (10 to 100 μg/mL) inhibited platelet aggregation and dense granule release induced by thrombin (0.05 U/mL), collagen (1 μg/mL), ionophore A23187 (2 μmol/L), ADP (12.5 μmol/L), and adrenaline (3.2 μmol/L). The inhibition of platelet aggregation by lysoPC was dose-dependent and correlated with decreased fibrinogen binding to glycoprotein IIb-IIIa. Our studies indicate that the enzymatic generation of lysoPC from plasma lipoproteins is essential for the sPLA2-mediated inhibition of platelet activation in the presence of albumin. These results raise the possibility that the toxic effects of circulating sPLA2 may be due in part to the generation of the bioactive lysophospholipid, lysoPC.

    Original languageEnglish
    Pages (from-to)4166-4174
    Number of pages9
    JournalBlood
    Volume86
    Issue number11
    Publication statusPublished - 1995

    Cite this

    @article{1743a7227a2446a38ef441a2997bdf1a,
    title = "An essential role for lysophosphatidylcholine in the inhibition of platelet aggregation by secretory phospholipase A2",
    abstract = "The release of secretory phospholipase A2 (sPLA2) into the mammalian circulation may contribute to the development of hemorrhagic and inflammatory diseases. sPLA2 has previously been shown to alter the behavior of platelets, leukocytes, and endothelial cells, although the molecular basis for these cellular effects has not been established. Our studies indicate that the inhibition of platelet aggregation by snake, bee venom, and pancreatic sPLA2 is dependent on a plasma cofactor. This cofactor resides within the lipoprotein fraction of plasma, with 54{\%}, 31{\%}, and 11{\%} of the activity present in the high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low density lipoprotein (VLDL) fractions, respectively. Delipidation of HDL and LDL was associated with the complete loss of platelet-inhibitory activity. Incubation of purified sPLA2 with the HDL fraction of plasma resulted in the time-dependent generation of lysophosphatidylcholine (lysoPC). The formation of lysoPC correlated with the inhibition of platelet aggregation. Purified lysoPC (10 to 100 μg/mL) inhibited platelet aggregation and dense granule release induced by thrombin (0.05 U/mL), collagen (1 μg/mL), ionophore A23187 (2 μmol/L), ADP (12.5 μmol/L), and adrenaline (3.2 μmol/L). The inhibition of platelet aggregation by lysoPC was dose-dependent and correlated with decreased fibrinogen binding to glycoprotein IIb-IIIa. Our studies indicate that the enzymatic generation of lysoPC from plasma lipoproteins is essential for the sPLA2-mediated inhibition of platelet activation in the presence of albumin. These results raise the possibility that the toxic effects of circulating sPLA2 may be due in part to the generation of the bioactive lysophospholipid, lysoPC.",
    author = "Y. Yuan and Jackson, {S. P.} and Newnham, {H. H.} and Mitchell, {C. A.} and Salem, {H. H.}",
    year = "1995",
    language = "English",
    volume = "86",
    pages = "4166--4174",
    journal = "Blood",
    issn = "0006-4971",
    publisher = "American Society of Hematology",
    number = "11",

    }

    An essential role for lysophosphatidylcholine in the inhibition of platelet aggregation by secretory phospholipase A2. / Yuan, Y.; Jackson, S. P.; Newnham, H. H.; Mitchell, C. A.; Salem, H. H.

    In: Blood, Vol. 86, No. 11, 1995, p. 4166-4174.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - An essential role for lysophosphatidylcholine in the inhibition of platelet aggregation by secretory phospholipase A2

    AU - Yuan, Y.

    AU - Jackson, S. P.

    AU - Newnham, H. H.

    AU - Mitchell, C. A.

    AU - Salem, H. H.

    PY - 1995

    Y1 - 1995

    N2 - The release of secretory phospholipase A2 (sPLA2) into the mammalian circulation may contribute to the development of hemorrhagic and inflammatory diseases. sPLA2 has previously been shown to alter the behavior of platelets, leukocytes, and endothelial cells, although the molecular basis for these cellular effects has not been established. Our studies indicate that the inhibition of platelet aggregation by snake, bee venom, and pancreatic sPLA2 is dependent on a plasma cofactor. This cofactor resides within the lipoprotein fraction of plasma, with 54%, 31%, and 11% of the activity present in the high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low density lipoprotein (VLDL) fractions, respectively. Delipidation of HDL and LDL was associated with the complete loss of platelet-inhibitory activity. Incubation of purified sPLA2 with the HDL fraction of plasma resulted in the time-dependent generation of lysophosphatidylcholine (lysoPC). The formation of lysoPC correlated with the inhibition of platelet aggregation. Purified lysoPC (10 to 100 μg/mL) inhibited platelet aggregation and dense granule release induced by thrombin (0.05 U/mL), collagen (1 μg/mL), ionophore A23187 (2 μmol/L), ADP (12.5 μmol/L), and adrenaline (3.2 μmol/L). The inhibition of platelet aggregation by lysoPC was dose-dependent and correlated with decreased fibrinogen binding to glycoprotein IIb-IIIa. Our studies indicate that the enzymatic generation of lysoPC from plasma lipoproteins is essential for the sPLA2-mediated inhibition of platelet activation in the presence of albumin. These results raise the possibility that the toxic effects of circulating sPLA2 may be due in part to the generation of the bioactive lysophospholipid, lysoPC.

    AB - The release of secretory phospholipase A2 (sPLA2) into the mammalian circulation may contribute to the development of hemorrhagic and inflammatory diseases. sPLA2 has previously been shown to alter the behavior of platelets, leukocytes, and endothelial cells, although the molecular basis for these cellular effects has not been established. Our studies indicate that the inhibition of platelet aggregation by snake, bee venom, and pancreatic sPLA2 is dependent on a plasma cofactor. This cofactor resides within the lipoprotein fraction of plasma, with 54%, 31%, and 11% of the activity present in the high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low density lipoprotein (VLDL) fractions, respectively. Delipidation of HDL and LDL was associated with the complete loss of platelet-inhibitory activity. Incubation of purified sPLA2 with the HDL fraction of plasma resulted in the time-dependent generation of lysophosphatidylcholine (lysoPC). The formation of lysoPC correlated with the inhibition of platelet aggregation. Purified lysoPC (10 to 100 μg/mL) inhibited platelet aggregation and dense granule release induced by thrombin (0.05 U/mL), collagen (1 μg/mL), ionophore A23187 (2 μmol/L), ADP (12.5 μmol/L), and adrenaline (3.2 μmol/L). The inhibition of platelet aggregation by lysoPC was dose-dependent and correlated with decreased fibrinogen binding to glycoprotein IIb-IIIa. Our studies indicate that the enzymatic generation of lysoPC from plasma lipoproteins is essential for the sPLA2-mediated inhibition of platelet activation in the presence of albumin. These results raise the possibility that the toxic effects of circulating sPLA2 may be due in part to the generation of the bioactive lysophospholipid, lysoPC.

    UR - http://www.scopus.com/inward/record.url?scp=0028825517&partnerID=8YFLogxK

    M3 - Article

    VL - 86

    SP - 4166

    EP - 4174

    JO - Blood

    JF - Blood

    SN - 0006-4971

    IS - 11

    ER -