Functional characteristics of in vitro generated macrophages: a transient refractory state precedes reinducibility of a spatially restricted, possibly contact-dependent, cytostatic mechanism

Adherent layers of macrophages (M phi-c) generated in vitro from splenic precursors previously have been shown to inhibit proliferation of normal and neoplastic cells by mechanisms that do not involve the secretion of significant quantities of prostaglandins, peroxides, or proteases. In the current report, it is demonstrated that the effective range of the cytostatic effect of adherent M phi-c is so low that cytostasis can be circumvented by preventing the target cells from settling to the adherent layer by incubating the cultures of targets and M phi-c on a rocking platform. Despite the paucity of production of inhibitory mediators, the M phi-c do produce sufficient IL-1 to restore IL-2 production capacity to macrophage-depleted lymphocyte populations. The cytostatic activity of the M phi-c is an inducible event and remains for several days in the continuous presence of mitogen-activated lymphocytes or LPS + lymphokines. Once the activators are removed the cytostatic activity rapidly declines, reaching background levels in 24-48 hr. Maximal cytostatic activity can be reinduced but only 48 hr or longer after the primary activators were removed. A transient period in which the M phi-c are refractory to reactivation can be demonstrated to exist for 1-2 days after removal of the primary activators.