Intercellular Interactions in the Interphase Death of Irradiated Thymocytes

Abstract

The effect of the interaction of different types of cells on the interphase death and pycnosis of thymocytes irradiated in vitro was studied. When removed from the thymus suspension of cells with natural killer activity, medullary thymocytes and macrophages did not change the radiation-induced death of cortical thymocytes. On the other hand, postirradiation incubation of cortical thymocytes together with unirradiated thymocytes or with cells of certain other cell lines diminished thymocyte death. Mixing the cell suspensions and changing the incubation medium decreased thymocyte death. All of these results indicate that these cells produce soluble mediators that are toxic to the cells that secrete them. The possible nature of these autotoxic mediators has been studied using inhibitors of arachidonic acid metabolism. Inhibitors of phospholipase A2 or lipoxygenase reduced interphase death markedly, while an inhibitor of cyclooxygenase did not. These data suggest that some lipoxygenase products may serve as autotoxic mediators in the interphase death of thymocytes.

Role of arachidonic acid metabolism in thymocyte apoptosis after irradiation

“…This control confirmed that NDGA affects apoptosis via lipoxygenase inhibition. Taken together these data and the apoptosis prevention with the PLA2 inhibitor [5,14] 1, control; 2, 6 Gy; 3, 6 Gy+l gM indomethacin; 4, 6 Gy+10 gM indomethacin; 5, 6 Gy+100 I.tM indomethacin; 6, 6 Gy+20 gM NDGA; 7, 40 gM NDGA; 8, 6 Gy+40 gM NDGA. n = 3~.…”

“…Previously we have shown that BPB, a PLA2 inhibitor [11], prevents nuclear pycnosis [5] and DNA fragmentation [14] in irradiated thymocytes. Nuclear pycnosis was the only criterion of the effects of lipoxygenase and cyclooxygenase inhibitors [5]. Nuclear pycnosis (or chromatin condensation) and intemucleosomal DNA fragmentation are *Corresponding author.…”

“…Apoptosis can be initiated by various inducers such as corticoids, quinone compounds, by triggering of cytokine receptors, deprivation of growth factors and ionizing radiation [3]. The apoptotic death of irradiated thymocytes is dependent on their interactions occurring via as yet unknown mediators [4,5]. The AA metabolites are likely candidates for this role.…”

“…The released AA is consequently oxidized either by cyclooxygenase with formation of cyclic products like prostaglandins, or by lipoxygenase giving rise to linear chain products such as lipoxines and leukotrienes [8,13]. Previously we have shown that BPB, a PLA2 inhibitor [11], prevents nuclear pycnosis [5] and DNA fragmentation [14] in irradiated thymocytes. Nuclear pycnosis was the only criterion of the effects of lipoxygenase and cyclooxygenase inhibitors [5].…”

Cloning and Characterization of Novel Mouse and Human Secretory Phospholipase A2s

“…During the progression of sepsis, thymic atrophy is induced via apoptosis (46). Because several reports suggest an involvement of PLA 2 in thymocyte apoptosis (47,48), the novel sPLA 2 might play a role in this process. The expression of novel sPLA 2 mRNA was also changed in rat lung after LPS treatment, but its pattern was different from the case of group IIA sPLA 2 .…”