This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ehrke, M. J. Articles by Mihich, E. Search for Related Content PubMed PubMed Citation Articles by Ehrke, M. J. Articles by Mihich, E.

Selectivity of Inhibition by Anticancer Agents of Mouse Spleen Immune Effector Functions Involved in Responses to Sheep Erythrocytes¹

Department of Experimental Therapeutics and Grace Cancer Drug Center, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, New York 14263

The selective effects of 24 agents on mouse spleen effector functions involved in the immune responses to sheep erythrocytes have been demonstrated. Five tests were used to assay the effector functions: the complement-dependent cellular cytotoxicity test, which measures complement-mediated lysis in the presence of antibody excreted from B-cell effectors; the complement-in-dependent cellular cytotoxicity test, which measures lysis after non-T-cell, non-B-cell interactions with target cells coated with antibody excreted by B-cells within the same spleen cell populations; the antibody-dependent cellular cytotoxicity test, which measures lysis after non-T-cell, non-B-cell interactions with antiserum-coated target cells; the complement-independent phagocytic test and the antibody-dependent phagocytic test, which measure phagocytosis of target cells coated with endogenous and added antibody, respectively. These five tests were, in general, insensitive to inhibitors of DNA synthesis. Phagocytosis and lysis associated with complement-independent cellular cytotoxicity were selectively sensitive to protein inhibitors, anthracycline antibiotics, bleomycin, actinomycin D, 2-deoxy-D-glucose, and N⁶-benzyladenosine. All functions, except complement-dependent cellular cytotoxicity, were inhibited by agents that affect cellular motility and/or membrane characteristics. The complement-dependent cellular cytotoxicity was only affected by agents that probably acted in a nonspecific cytotoxic manner. Potentiation of immune function was demonstrated in one case, namely, with N⁶-(²-isopentenyl)adenosine. The demonstrated selectivity of action of the agents studied in vitro permitted speculation concerning the cellular effector functions involved in the efferent arm of the mouse spleen cell response to sheep erythrocytes and indicated selectivities on cellular functions that may become relevant in vivo.

¹ This investigation was supported in part by USPHS Grants CA-15142 and CA-13038.

² Present address: S. Farber Cancer Center, Division of Tumor Immunology, Boston, Mass. 02115.

Received 11/23/76. Accepted 11/17/77.