Modifications Induced by Activation to Tumor Cytotoxicity in the Protein Secretory Activity of Macrophages

Abstract

After biosynthetic radiolabeling, polypeptides secreted by macrophages were analyzed by electrophoresis on polyacrylamide gels in the presence of sodium dodecyl sulfate and fluorography. Comparative studies of various macrophage populations (inflammatory macrophages, primed and activated macrophages, resident macrophages) showed that secretory activity is elaborately controlled according to macrophage developmental and functional state. When young macrophages activated to cytotoxicity against tumor cells by an appropriate eliciting agent and culture in the presence of lipopolysaccharide were compared to mature resident macrophages devoid of antitumor activity, the following changes were observed in the protein secretion phenotype: (1) New polypeptides are expressed: the intensity of four bands was increased more than five-fold on one-dimensional gels and 17 new spots were detected on two-dimensional gels. (2) The production of several major polypeptides is repressed: six bands were strongly decreased on one-dimensional gels, and 11 major spots (or groups of spots) were lost on two-dimensional gels. (3) The charge microheterogeneity pattern exhibited by several polypeptides on two-dimensional gels is shifted towards less acidic species.

Natural and synthetic trehalose diesters as immunomodulators

“…l~~ Four polypeptides (Mr = 44.5, 36, 22 and 20) were specifically detected in media conditioned by TDM-or BCG-activated macrophages. 127 Analysis on two-dimensional gels revealed further differences: 12 spots were specific for activated macrophages and there was a shift of several glycoproteins to less acidic specie^. "^…”

Adjuvant effects of trehalose dimycolate on the antibody response to type III pneumococcal polysaccharide

“…Although the mechanism by which TDM prevents induction of low-dose paralysis is not known, the ability of TDM to increase the extent to which B cells proliferate in response to an antigen could play a significant role; however, the possibility has not been excluded that TDM can also stimulate amplifier T cells which interact with suppressor T cells in an opposing and competitive manner to regulate the magnitude of the antibody response to SSS-III (reviewed in reference 7). In this context, TDM has been reported to augment T-cell proliferation (21) and some T-cell functions such as synthesis of interferon (2) and expression of delayed-type hypersensitivity (28); however, the effects of TDM on macrophages have been well documented (16,22) and it is known to stimulate macrophages to synthesize and release a variety of soluble products, most of which have not been characterized (18,19). The extent to which these endogenous products can influence the expression of B-cell and/or regulatory T-cell function remains to be determined.…”