Role of interleukin-2 and mononuclear cells in platelet-tumor interactions.
Interleukin-2 (IL-2) has been reported to induce mononuclear cell-dependent platelet perturbations and to reduce the incidence of metastases in rodent models. In this study, MC-1 leukemic cell-induced platelet aggregation was associated with a significant increase in thromboxane B2 (TXB2) secretion, quantified by RIA, but a decrease in leukotriene B4 (LTB-4) secretion compared to incubations of tumor cells alone. Whereas MC-1 cells also activated platelets as observed by a significant increase in scanning electron-microscopic spheroidal forms distributed throughout the platelet pool, increasing concentrations of IL-2-activated peripheral blood mononuclear cells (PBMC), but not IL-2 or PBMC alone, reversed this effect with a reduction in activated spheroidal forms. The addition of IL-2-activated PBMC to MC-1 platelet incubations inhibited platelet-tumor cell adhesion and suppressed MC-1-induced aggregation. In order to investigate the mechanism resulting in inhibition of MC-1-induced platelet aggregation, short-term PRP-MC-1 preparations were incubated with IL-2-activated PBMC and assayed for TXB2 and LTB-4 by RIA. LTB-4 levels were significantly elevated in these preparations while levels of TXB2 were significantly reduced compared with control platelet-rich plasma (PRP)-MC-1 incubations. Our results showed that inhibition of MC-1-induced platelet activation, aggregation and tumor-platelet adhesion by the addition of IL-2-activated PBMC was consequent to a cellular effect of IL-2 on PBMC. These findings may be important in understanding the observed antimetastatic effect of IL-2.
Oleksowicz
L
L
Department of Medical Oncology, Montefiore Hospital and Medical Center, Albert Einstein College of Medicine, Bronx, NY
Zuckerman
D
D
Lomazova
K D
KD
Buryachkofska
L E
LE
Astrina
O C
OC
Slavina
E G
EG
D000328:Adult; D002449:Cell Aggregation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D015458:Leukemia, T-Cell / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology*; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D008855:Microscopy, Electron, Scanning; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D011863:Radioimmunoassay; D013929:Thromboxane B2 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D007975:Leukotriene B4; D013929:Thromboxane B2