Morphologic and ultrastructural evidence of interleukin-6 induced platelet activation.
The in vitro effect of IL-6 on platelet activation was investigated. When human platelets were incubated with high (1,000 ng/ml) or low (1 ng/ml) dose IL-6, expression of GMP-140 was enhanced by 42% (N = 6; P < 0.009) and 46% (N = 6; P < 0.061) in 1 hr low and high dose IL-6-platelet incubations, respectively, as assessed by flow cytometry. In platelet specimens incubated with high dose IL-6 for 3 hr, a 70% (N = 6; P < 0.009) increase in GMP-140 expression over control was observed. Parallel high dose IL-6 incubations subjected to scanning electron microscopic studies revealed a 3.4-fold increase (N = 6; P < 0.001) in spheroid morphologic platelet forms in 1 hr incubations in comparison to control platelet preparations, whereas in 3 hr IL-6-platelet incubations, a 96% increase in dendritic platelet forms was observed (N = 6; P < 0.001). Significant increases in platelet ATP levels were observed in both 1 min and 1 hr high dose and low dose IL-6 platelet incubations. In 3 hr high dose-IL-6 platelet incubations, a significant 18% (N = 8; P < 0.001) decrease in platelet ATP was parallelled by a significant 40% increase (N = 8; P < 0.014) in plasma ATP in the same specimens. This increased plasma ATP was highly correlated with a reduction in platelet ATP when analyzed by bivariate regression analysis. Lastly, transmission electron microscopic analysis demonstrated a significant reduction in dense granule number and ratio of dense granule surface area/cell surface area in 3 hr high dose IL-6 incubations. These findings suggests that IL-6 activates platelets in vitro.
Oleksowicz
L
L
Department of Oncology, Montefiore Medical Center Hospital, Albert Einstein College of Medicine, Bronx, New York 10467.
Mrowiec
Z
Z
Isaacs
R
R
Dutcher
J P
JP
Puszkin
E
E
D000255:Adenosine Triphosphate / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure*; D015815:Cell Adhesion Molecules / Q000097:blood; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D019007:P-Selectin; D015539:Platelet Activation; D010980:Platelet Membrane Glycoproteins / Q000097:blood; D011994:Recombinant Proteins / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D015850:Interleukin-6; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate