Naturally occurring lymphocytes, macrophages, and other leukocytes and their secretory products (e.g., lymphokines, interleukins, and other immunological hormones), are being studied to define their effective anticarcinogenic and tumor cell growth inhibitory activities. Leukoregulin, a newly isolated lymphokine, can prevent carcinogenesis and inhibit tumor cell growth. Anticarcinogenic action is direct and irreversible and occurs without cytotoxicity. Inhibition of tumor cell growth is primarily reversible but can become irreversible due to increased susceptibility of preneoplastic and neoplastic cells to cytolytic destruction by natural killer cells resulting from leukoregulin target cell interaction. Leukoregulin at very high concentrations is also directly cytolytic for tumor cells. The direct acting anticarcinogenic activity of leukoregulin is more potent than the tumor cell inhibitory activity; but by also being able to increase target cell sensitivity to the cytoreductive action of naturally cytotoxic lymphocytes, the lymphokine may be an effective homeostatic mechanism for control of carcinogenesis at its later stages of development. Leukoregulin anticarcinogenic, tumor cell growth inhibitory, and cytoreductive sensitizing activity co-purify into two major glycoprotein classes with different isoelectric pHs. The more acidic class has an isoelectric pH of 4.6 and 5.0 and the other class an isoelectric pH of 5.0 and 7.1 for hamster and human leukoregulin, respectively. The anti-cancer actions of leukoregulin are distinct from other lymphokines including interleukin I, interleukin II, lymphotoxin, macrophage migration inhibitory factor, macrophage activating factor, and interferon. Leukoregulin alters cell surface conformation, membrane fluidity and permeability, and large molecular weight membrane glycoprotein synthesis with changes in the latter correlating directly in time and quantity to leukoregulin induced establishment of the anticarcinogenic state. Leukoregulin induces identical changes in target cells that are present during natural killer cell cytotoxicity providing strong evidence that it is an intrinsic mediator or element of the natural cytotoxicity reaction and possibly signifying its central role in immunological homeostasis.
NIH ExPorter
NIH ExPorter