Macrophage Activation by Cross-Linked Dextran

Abstract

Cross-linked dextran (Sephadex) has been reported as an effective inducer of peritoneal exudates resulting in a large yield of macrophages after injection into mice, and macrophages obtained in this manner have been used for a variety of studies. We examined the possibility that cross-linked dextran not only induces peritoneal exudate but functions also as a macrophage activator. Following confirmation of a markedly increased yield of macrophages in Balb/c mice injected with preswollen Sephadex G-25 beads, glass adherence and migration in agarose of these macrophages were compared with the activities of cells isolated following the injection of saline, thioglycollate, or complete Freund's adjuvant (CFA). Dextran administration resulted in a significant increase in these activities in relation to saline and thioglycollate injections, and resembled CFA in the magnitude of its effect. Dextran-induced macrophages were then examined for activation as defined by nonspecific antitumor activity. Cells of a transplantable fibrosarcoma line and a urethane-induced primary lung adenoma served as targets. As compared with macrophages isolated from saline-injected mice, cells induced by Sephadex showed an approximately fivefold and twofold increase in activity against adenoma and fibrosarcoma targets, respectively. To examine the ability of Sephadex to induce macrophage antitumor activity in vitro, peritoneal macrophages were cultured in the presence of the dextran for 24 hours and tested against adenoma targets. The tumoricidal/static activity of such macrophages was significantly increased relative to controls and was nearly identical to the activity of macrophages induced by Sephadex in vivo. It is clear that cross-linked dextran in the form of Sephadex G-25 can function both as an inducer of peritoneal exudate and as an effective macrophage activator with regard to the activation criteria studied.

Theranostic Nucleic Acid Binding Nanoprobe Exerts Anti-inflammatory and Cytoprotective Effects in Ischemic Injury

“…Control amino-dextran (without TO) caused an unexpected, but mild, increase in cytokine production. This is consistent with prior reports of immune stimulation by dextran in mice 17-19. Of note, the same amino-dextran preparation was used to synthesize Dex-TO, making the large reductions in cytokine production produced by Dex-TO even more noteworthy.…”

Macrophage Stimulation with Some Structurally Related Polysaccharides

“…Recently. Blanckmeister et al showed that crosslinked dextran {1,6-a-glucan) could stimulate macrophages in vivo to become cytotoxic in vitro [5]. However, these investigators did not determine the purity of their macrophage cultures.…”

“…It is therefore conceivable that the stimulatory effect of the 1.3->9-glucans is due to the particulate and rigid state of these molecules and hence other watersoluble polysaccharides when presented to the macrophages in particulate form would be as stitnulutory as the 1,3-jtf-glucans. Indeed, a recetit report suggests that particulate 1.6-a-glucan (dextran) can activate peritoneal macrophages to kill ttimour cells in vitro [5],…”

Aging and eliciting agents: Effect on murine peritoneal macrophage monokine bioactivity

“…This variation in experiments assessing monokine production by the aged might relate to differences in technique, especially methods to obtain macrophages. Different agents used to elicit peritoneal macrophages for study have been shown to alter macrophage function (Edelson et al, 1975;Johnston et aL, 1978;North, 1978;Ruco and Meltzer, 1978;Hopper and Geczy, 1980;Ogmundsdottir, 1980;Spitalny, 1981;Rasmussen et al, 1983;Leijh et aL, 1984;Blanckmeister and Sussdorf, 1985;Hopper, 1986;Tannenbaum et aL, 1987;Melnicoff et al, 1989;Higuchi et al, 1990;Reed and Burnham, 1991;Tomioka and Saito, 1992) and possibly monokine production (Marcinkiewicz, 1991) through mechanisms that are not yet well defined. In this study, the effects of various eliciting agents, complete Freund's adjuvant (CFA), thioglycollate (TG), or no treatment, on IL-l, IL-6, and TNF bioactivity in peritoneal macrophage supernatants from young, middle aged, and aged mice was assessed.…”