Enhancement of human platelet activation by the combination of low concentrations of collagen and rabbit anticardiolipin antibodies.
Low concentrations of collagen and anticardiolipin antibodies (ACLA), which were raised in rabbits by immunization with cardiolipin (CL), co-operatively activated human gel-filtrated platelets (GFP). GFP activated by adding ACLA 5 min prior to collagen (ACLA + Col) showed strong responses in cytosolic Ca2+ mobilization and cell aggregation; the responses decreased after 1 min, however, when collagen was added prior to ACLA (Col + ACLA). Col + ACLA was 30% less effective than the ACLA + Col in: (1) the phosphorylation of pleckstrin and myosin light chain; and (2) the secretion of alpha- and dense granules. Indomethacin inhibited Ca2+ mobilization, pleckstrin phosphorylation and cell aggregation in platelets stimulated by ACLA + Col. The thromboxane B2 level in platelets induced by ACLA + Col was similar to that stimulated by low concentrations of collagen alone. ACLA + Col increased the activities of phospholipase C (PLC) as determined by formation of phosphatidic acid (PA), whereas indomethacin and adenosine 2',5'-diphosphate, an antagonist of the ADP P2Y1 receptor, inhibited PA formation. These results suggest that ACLA, thromboxane A2 derived from the collagen pathway and secreted ADP co-operatively augment PLC activity and lead to platelet aggregation.
Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan.
Lai
L
Wang
Chen-Yi
CY
Su
Kuang-Yu
KY
Chou
Cheng-Teh
CT
Wang
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000494:pharmacology*; D001798:Blood Proteins / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D018994:Myosin Light Chains / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation; D011817:Rabbits; D013929:Thromboxane B2 / Q000378:metabolism; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism
D017153:Antibodies, Anticardiolipin; D001798:Blood Proteins; D016861:Cyclooxygenase Inhibitors; D018994:Myosin Light Chains; D010750:Phosphoproteins; C039077:platelet protein P47; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D003094:Collagen; D010738:Type C Phospholipases; D007213:Indomethacin