Macrophage-mediated natural cytotoxicity against various target cells in vitro. II. Macrophages from rats of different ages

Abstract

Summary.-Adherent, predominantly phagocytic mononuclear cells from various rat tissues express spontaneous cytotoxicity against diverse target cells in vitro. The extent to which cytotoxicity was expressed by effector cells depended on the age of donors. Cytolytic effector-cell capacity was already fully developed a few days after birth, and persisted over many months, but was clearly reduced in senescence. Similarly, the ability to intensify natural cytotoxicity by peptone in vivo was already fully manifested in the newborn, but was significantly diminished in old rats.

Competition between foetal tissue and macrophage-dependent natural tumour resistance

“…2 (2-3 months of age) augmentation of tumour growth was much less impressive (3/6 experiments) or even lacking (1/6). It is noteworthy that in the present model system, spontaneous tumour resistance has been found highest in the youngest age group examined (30 days), was slightly lower in rats aged 3-4 months, and was consistently reduced in rats aged 12-18 months (Keller, 1978a). The time dependence of the tumourpromoting effect of foetal tissues was ascertained by inoculation at various intervals before or after tumour-cell challenge.…”

“…Moreover, the consequences of the interaction between macrophages and nonproliferating foetal and/or adult liver cells were also assessed with the [3H]-proline were added. After 36 h, radioactivity was measured in sediments and supernatants, and calculated as described in Keller, 1978b. Two different controls wNere included: (a) medium control containing only labelled target cells ("spontaneous release"), and (b) autologous control containing unlabelled targets in place of, and at the same concentration as, effector cells (Keller & Keist, 1978).…”

Tumour-promoting diterpene esters prevent macrophage activation

“…After intensive washing, Accepted 30 September 1981 the cells remaining adherent were used as a source of effector cells (Keller, 1978). To enhance their non-specific cytolysis the resting adherent peritoneal cells were interacted for 8 h with macrophageactivating lymphokines (MAL; a cell-free supernatant from 72h cultures of rat spleen cells in serum-free RPMI-1640 medium supplemented with 5 Hg/ml concanavalin A (Sigma); final concentration 20%) and then washed.…”

“…To enhance their non-specific cytolysis the resting adherent peritoneal cells were interacted for 8 h with macrophageactivating lymphokines (MAL; a cell-free supernatant from 72h cultures of rat spleen cells in serum-free RPMI-1640 medium supplemented with 5 Hg/ml concanavalin A (Sigma); final concentration 20%) and then washed. DA rat polyomainduced tumour cells (Keller, 1978) were used as target cells, having been prelabelled with [14C]-dT (methyl-14C-dT 40-60 mCi/mmol; New England Nuclear, Boston, Mass.) as previously described (Keller & Keist, 1978) and then interacted with effector cells for 36 h at 37°C (initial effector/target cell ratio 10: 1).…”

“…as previously described (Keller & Keist, 1978) and then interacted with effector cells for 36 h at 37°C (initial effector/target cell ratio 10: 1). The released radioactivity was then measured and net cytotoxicity calculated (Keller, 1978).…”