Defect in regulation of Ca²⁺ movement in platelets from patients with systemic lupus erythematosus

The differences in the intracellular Ca²⁺ responses to hormones in platelets from systemic lupus erythematosus (SLE) patients compared to normal humans have not been explored. This study examined the Ca²⁺ signaling and density of platelets in normal, inactive and active SLE patients. The platelet number per μl 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 Ca²⁺ levels ([Ca²⁺] _i) in response to stimulation of four endogenous Ca²⁺ mobilizing hormones, 100 μM arachidonic acid (AA), 10 μM ADP, 10 nM platelet activation factor (PAF) and 1 μM thrombin, were investigated using the Ca²⁺-sensitive fluorescent dye, fura-2. The AA-induced [Ca ²⁺], rises in normal and inactive groups were similar. In contrast, the AA-induced [Ca²⁺], rises in the active SLE group were significantly smallerthan in the normal and inactive groups. The defect in the AA-induced [Ca²⁺], rises in active SLE groups appears to be caused by defective Ca²⁺ influx and Ca²⁺ 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 Ca²⁺, and the AA-induced Ca²⁺ release was smaller in the active SLE group. PAF, ADP and thrombin all induced [Ca²⁺]_i rises in the three groups, but no significant differences were found among the three groups. Together, the results indicate that cell density and Ca²⁺ 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.