The immunosuppressive effects of antileukemic asparaginases isolated from Escherichia coli and Erwinia carotovora are well documented, but the basis for the immunosuppression is unclear. In addition to catalyzing the deamination of l-asparagine, the E. coli and E. carotovora enzymes also deaminate l-glutamine (glutaminase activity). Many investigators have suggested that this glutaminase activity may be the cause of immunosuppression. The role of glutaminase activity in this immunosuppression has been difficult to evaluate, largely because the lack of a glutaminase-free asparaginase obtainable in significant quantity has precluded any rigorous in vivo experimentation. This laboratory has isolated an asparaginase from Vibrio succinogenes which has potent antilymphoma activity and lacks glutaminase activity. In the present communication, we report the effects of treatment with E. coli and V. succinogenes asparaginases on specialized immune responses in BALB/cCrgl mice.

The immunosuppressive effects of E. coli and V. succinogenes asparaginase on the humoral response of mice during sheep red blood cell (SRBC) immunization were investigated using the plaque-forming cell assay. There was a marked reduction in the number of IgM and IgG plaque-forming cells in the E. coli asparaginase-treated group. No reduction in the plaque-forming cell response was observed in the V. succinogenes asparaginase-treated mice. Levels of antibody against SRBC as determined by hemagglutination were also depressed in E. coli asparaginase-treated mice. Splenocytes isolated from mice immunized with SRBC and simultaneously treated with asparaginase were tested for their capability to serve as effector cells in a direct-target killing assay using 51Cr-labeled SRBC's. At all concentrations tested, the E. coli enzyme significantly suppressed the cytotoxic response of splenocytes, while splenocytes from mice treated with V. succinogenes asparaginase maintained control levels of cytotoxicity. The data provide evidence that a glutaminase-free asparaginase from V. succinogenes does not suppress the in vivo immune response of mice to SRBC as compared to the pronounced immunosuppressive effects observed in mice treated with E. coli asparaginase.

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Supported by Grants IN-51P and IN-51Q from the American Cancer Society, Grant F79UM-1 from the Florida Division of the American Cancer Society (Jeffrey Frohman Research Grant), and grants from the United Way and the Women's Cancer Association of the University of Miami.

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