Hemoglobin A0 and alpha-crosslinked hemoglobin (alpha-DBBF) potentiate agonist-induced platelet aggregation through the platelet thromboxane receptor.
Chemically modified hemoglobins are potential oxygen-carrying blood substitutes, but their in vivo administration has been associated with a variety of unexpected side events, including increased platelet reactivity. We studied the effects of hemoglobin A0 (HbA0) and alpha-crosslinked hemoglobin (alpha-DBBF) on platelets in vitro. Neither hemoglobin A0 nor alpha-DBBF activated platelets when added alone, but both proteins potentiated submaximal agonist-induced platelet aggregation without increasing other markers of platelet activation such as serotonin secretion. Only agonists that are known to cause release of platelet arachidonic acid (AA) were potentiated while aggregation induced by ADP, which does not release AA, was not potentiated. Blockade of the thromboxane receptor with SQ-29,548 prevented the HbA0-induced and the alpha-DBBF-induced potentiation suggesting that the AA/thromboxane signaling pathway mediates the interaction of platelets with hemoglobin.
Mondoro
T H
TH
Laboratory of Cellular Hematology, Center for Biologics Evaluation and Research, FDA, Bethesda, MD 20892, USA.
Alayash
A I
AI
Ryan
B A
BA
Terle
D A
DA
Vostal
J G
JG
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000819:agonists; D016718:Arachidonic Acid / Q000819:agonists / Q000378:metabolism; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001792:Blood Platelets / Q000737:chemistry*; D001802:Blood Substitutes / Q000494:pharmacology; D003094:Collagen / Q000819:agonists / Q000187:drug effects; D004357:Drug Synergism; D006418:Heme / Q000494:pharmacology; D006441:Hemoglobin A / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects; D011982:Receptors, Prostaglandin / Q000187:drug effects; D017482:Receptors, Thromboxane / Q000097:blood*; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D015290:Second Messenger Systems / Q000187:drug effects; D013917:Thrombin / Q000187:drug effects / Q000378:metabolism
D001802:Blood Substitutes; D008565:Membrane Proteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; C103813:bis(3,5-dibromosalicyl)fumarate-crosslinked hemoglobin A(0); D016718:Arachidonic Acid; D006418:Heme; C028881:hemoglobin A(0); D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen; D006441:Hemoglobin A; D013917:Thrombin; D001241:Aspirin