Studies on the mechanism of Polyactin A's enhancive effect on NK cell activity

It has been shown that the novel immunopotentiator Polyactin A (PAA) developed in China can augment NK cell activity. In order to further understand the mechanism of PAA effect on NK activities, we measured the binding and lytic capacities of peripheral blood lymphocytes (PBL) isolated from normal subjects and patients with esophageal carcinoma against K₅₆₂ target cells by using a single cell cytotoxicity assay. Morphologically the ultrastructures of NK cells of normal subjects and the patients on PAA were also studied. The results showed that: (1) Preincubation PBL of normal subjects on PAA at 100 μg/ml for 4 hours could increase the rate of NK lysis with no effect on the binding rate. The binding capacities of PBL of patients with esophageal carcinoma were lower than those of normal subjects. Pretreatment PBL of patients with esophageal carcinoma could significantly increase not only the rate of NK lysis, but also the binding rate. (2) Study on the processes of conjugation and cytolysis by using light microscopic morphology, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) found that effector cells include not only large granular lymphocytes (LGL), but also non-LGL bound to target cells. One effector cell could simultaneously make contacts with more than one target cell. It was found that PBL/K₅₆₂ contacts could be morphologically divided into two types in the SEM and TEM. Either effector cell protrusions were pushed deep into pouches and lacunae of the target cell surface or a wide area of intimate cell to-cell contact was formed. Effector/target cell contact is a prerequisite for NK lytic activity. After the formation of contact, alterations of the target cell followed. During the disintegration stage, internal vacuolization and swelling of cytoplasmic organelles, particularly welling of mitochondria occurred. Eventually, karyopyknosis, karyothecalysis, and honeycomb occurred in the target cell. Sometimes local cytopathogenic membrane or cytoplasmic changes were observed in the contact areas. In conclusion, the lysis of NK targets may be due to not only the direct contact between effector and target cells, but also NK lytic factors.