RECOMBINANT MURINE GAMMA-INTERFERON STIMULATES MACROPHAGES OF THE RAW CELL-LINE TO INHIBIT INTRACELLULAR GROWTH OF HISTOPLASMA-CAPSULATUM

被引:49
作者
NAKAMURA, LT [1 ]
WUHSIEH, BA [1 ]
HOWARD, DH [1 ]
机构
[1] UNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USA
关键词
D O I
10.1128/IAI.62.2.680-684.1994
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Macrophages of the RAW 264.7 cell line, activated by pretreatment with recombinant murine gamma interferon, inhibit the intracellular growth of Histoplasma capsulatum. Growth inhibition occurred by a mechanism that was operative only when L-Arg metabolism was allowed to occur. When activated macrophages were cultured in the absence of L-Arg or in the presence of N-G-monomethyl-L-Arg, a competitive inhibitor of L-Arg metabolism, activation to the antihistoplasma growth-inhibitory state did not occur. An increase in levels of NO2-, an end product of L-Arg metabolism, was detected only after activation of RAW 264.7 cells to the growth-inhibitory state. In contrast, only baseline levels of NO2- were detected when L-Arg was excluded or when N-G-monomethyl-L-Arg was added to the culture medium. Nitric oxide (NO .), a reactive intermediate product of L-Arg metabolism, was implicated as the relevant antihistoplasma effector molecule. When H. capsulatum yeast cells were cultured for 24 to 28 h in a system designed to generate soluble NO ., a dose-dependent cytotoxic effect was observed.
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页码:680 / 684
页数:5
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