Abstract |
Macrophages (M phi)3 function by a two-step process that includes priming (induction of cytokine and enzyme mRNA) and activation (production of effector molecules). The initial steps in M phi priming involve the expression of certain proto-oncogenes that regulate expression of other genes. Because tumor growth primes M phi to produce several suppressor monokines, we determined if cancer induced M phi expression of these proto-oncogenes. Unstimulated peritoneal M phi from tumor-bearing hosts (TBH) constitutively expressed the proto-oncogenes c-fms, c-fos, c-myc, and c-myb, whereas normal host (NH) M phi had little or no expression of these proto-oncogenes. When M phi were given a 24-h adherence priming stimulus, NH M phi expressed c-fms and c-fos at levels equivalent to TBH M phi constitutive expression. Adherence had little or no effect on c-fms and c-fos expression in TBH M phi or on NH and TBH M phi c-myc expression. c-myb expression was not induced in NH M phi during adherence and was strongly decreased in TBH M phi. Activation with a 1-h lipopolysaccharide-treatment increased NH and TBH M phi expression of c-fms, c-fos, and c-myc, with higher expression of these proto-oncogenes in TBH M phi. Activation failed to induce c-myb expression in NH M phi and completely inhibited expression in TBH M phi. Because c-fms, c-fos, and c-myc are normally expressed early during M phi activation, our results suggest that tumor growth primes M phi by inducing expression of these proto-oncogenes. c-myb is expressed in immature M phi and is downregulated during M phi activation. These observations explain why NH M phi expression of c-myb was not induced and are consistent with reports that suggest TBH M phi have not reached full developmental maturity. The induction of M phi proto-oncogene expression during cancer may put M phi in a primed state, which leads to earlier and stronger production of adverse suppressor and cytotoxic molecules.
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Authors | D G Alleva, D Askew, C J Burger, K D Elgert |
Journal | Immunological investigations
(Immunol Invest)
Vol. 23
Issue 6-7
Pg. 457-72
(Nov 1994)
ISSN: 0882-0139 [Print] England |
PMID | 7851963
(Publication Type: Journal Article)
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Chemical References |
- Lipopolysaccharides
- Proto-Oncogene Proteins
- Proto-Oncogene Proteins c-myb
- RNA, Messenger
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Topics |
- Animals
- Fibrosarcoma
(immunology, pathology)
- Gene Expression
- Genes, fms
(genetics)
- Genes, fos
(genetics)
- Genes, myc
(genetics)
- Lipopolysaccharides
- Macrophage Activation
(immunology)
- Macrophages, Peritoneal
(immunology)
- Male
- Mice
- Mice, Inbred BALB C
- Proto-Oncogene Proteins
(biosynthesis, genetics)
- Proto-Oncogene Proteins c-myb
- Proto-Oncogenes
(genetics)
- RNA, Messenger
(biosynthesis, genetics)
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