Defect in regulation of Ca2+ movement in platelets from patients with systemic lupus erythematosus.
The differences in the intracellular Ca(2+) responses to hormones in platelets from systemic lupus erythematosus (SLE) patients compared to normal humans have not been explored. This study examined the Ca(2+) signaling and density of platelets in normal, inactive and active SLE patients. The platelet number per mul in inactive and normal groups did not differ, whereas the number in active SLE patients was smaller than the other two groups by 60%. The intracellular free Ca(2+) levels ([Ca(2+)](i)) in response to stimulation of four endogenous Ca(2+) mobilizing hormones, 100 microM arachidonic acid (AA), 10 microM ADP, 10 nM platelet activation factor (PAF) and 1 microM thrombin, were investigated using the Ca(2+)-sensitive fluorescent dye, fura-2. The AA-induced [Ca(2+)](i) rises in normal and inactive groups were similar. In contrast, the AA-induced [Ca(2+)](i) rises in the active SLE group were significantly smaller than in the normal and inactive groups. The defect in the AA-induced [Ca(2+)](i) rises in active SLE groups appears to be caused by defective Ca(2+) influx and Ca(2+) releasing pathways because the AA-induced responses were not altered by removal of extracellular Ca(2+), whereas the AA-induced responses in normal and inactive SLE groups were reduced by removal of extracellular Ca(2+), and the AA-induced Ca(2+) release was smaller in the active SLE group. PAF, ADP and thrombin all induced [Ca(2+)](i) rises in the three groups, but no significant differences were found among the three groups. Together, the results indicate that cell density and Ca(2+) signaling in platelets from active SLE patients are altered in response to particular stimulators. In these regards, platelets from inactive SLE patients appear to be similar to those from normal humans.
Cheng
He-Hsiung
HH
Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Ho
Chin-Man
CM
Huang
Chun-Jen
CJ
Hsu
Shu-Shong
SS
Jiann
Bang-Ping
BP
Chen
Jin-Shyr
JS
Huang
Jong-Khing
JK
Chang
Hong-Tai
HT
Lo
Yuk-Keung
YK
Yeh
Jeng-Hsien
JH
Jan
Chung-Ren
CR
D000244:Adenosine Diphosphate / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D016257:Fura-2 / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000378:metabolism / Q000503:physiopathology; D010361:Patients; D010972:Platelet Activating Factor / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D005456:Fluorescent Dyes; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D013917:Thrombin; D002118:Calcium; D016257:Fura-2