A defect of platelet release reaction in a patient with SLE: impaired platelet aggregation induced by phorbol ester with a normal phosphorylation of 40K protein.
A 37-year-old female who suffered from SLE had a bleeding disorder. At the time of initial evaluation, the main disease demonstrated was a delta-storage pool deficiency. After this improved, a marked decrease of aggregation still remained, when induced by either ADP, epinephrine, collagen, A23187, thrombin, or PAF-acether. Although arachidonate-induced aggregation was slightly decreased, thromboxane B2 was produced normally in response to exogenous arachidonate. The patient's endoperoxides and/or thromboxane A2 aggregated aspirin-treated platelets, though her platelets were themselves unresponsive. Impaired aggregability induced by TPA (12-0-tetradecanoylphorbol-13-acetate) or OAG (1-oleoyl-2-acetyl-glycerol) was also found. However, the phosphorylation of P43 and P20 induced by several stimulators including CA++ ionophore was normal, using 32P-labelled platelets. It is suggested that TPA or OAG-induced platelet aggregation requires not only the phosphorylation of those proteins, but also another unknown mechanism after the phosphorylation, and that the platelet dysfunction of this patient was due to a defect of some mechanism involving Ca++ uptake or mobilization of cytoplasmic Ca++ from intracellular storage sites.
Fuse
I
I
Hattori
A
A
Higashihara
M
M
Takizawa
S
S
Takeshige
T
T
Hanano
M
M
Nagayama
R
R
Koike
T
T
Takahashi
H
H
Shibata
A
A
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D001798:Blood Proteins / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood*; D010704:Phorbols / Q000494:pharmacology*; D010766:Phosphorylation; D010972:Platelet Activating Factor / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology
D001095:Arachidonic Acids; D001798:Blood Proteins; D004075:Diglycerides; D010704:Phorbols; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; D000001:Calcimycin; D000244:Adenosine Diphosphate; C038237:1-oleoyl-2-acetylglycerol; D003094:Collagen; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; D004837:Epinephrine