Rapid recruitment of macrophages in interleukin-12-mediated tumour regression

Sang-Jun Ha, S. B. Lee, C. M. Kim, H. S. Shin, Y. C. Sung

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

In order to study the mechanism of interleukin-12 (IL-12) antitumour activity, RH7777 rat hepatoma cells were engineered to express mouse IL-12 (miL-12) (RH7777/mIL-12) under the tight control of doxycycline (dox). The production of the mIL-12 protein was regulated by the concentration of dox that was present in the culture medium. RH7777/mIL-12 cells appeared to have the same tumorigenic activity as did parental RH7777 cells, when subcutaneously injected into syngeneic rat (BUF/N) in the absence of dox. However, the tumorigenicity of RH7777/mIL-12, but not RH7777, cells were significantly decreased when dox was administrated to the animals. In addition, established tumours of RH7777/mIL-12 cells gradually disappeared upon the induction of mIL-12 by dox. To elucidate the kinetic profile of immune cells involved in the mIL-12-induced tumour regression, both histological and immunohistochemical analyses were performed 1, 3 and 14 days after the dox treatment on rats bearing tumours that were approximately 0.5 cm in diameter. Tumour-infiltrating macrophages began to appear at the tumour site one day after dox treatment. As time elapsed, the number of tumour infiltrates including CD4+, CD8+, natural killer (NK) cells and macrophages gradually increased. In particular, CD8+ and NK cells constituted the major population of the tumour-infiltrated cells. Furthermore, it was found that resting peritoneal macrophages (PM) from rats were chemoattracted in response to mIL-12. The effects of mIL-12 on PM chemotaxis were reproducibly observed in concentrations as low as 0.1 ng/ml. These findings suggest that IL-12 can directly recruit macrophages into tumour sites which, in turn, leads to a broad and intense immunological response against tumour.

Original languageEnglish
Pages (from-to)156-163
Number of pages8
JournalImmunology
Volume95
Issue number1
DOIs
Publication statusPublished - 1998 Sep 15

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Interleukin-12
Doxycycline
Macrophages
Neoplasms
Peritoneal Macrophages
Natural Killer Cells
Inbred BUF Rats
Chemotaxis
Culture Media
Hepatocellular Carcinoma
Therapeutics

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Ha, Sang-Jun ; Lee, S. B. ; Kim, C. M. ; Shin, H. S. ; Sung, Y. C. / Rapid recruitment of macrophages in interleukin-12-mediated tumour regression. In: Immunology. 1998 ; Vol. 95, No. 1. pp. 156-163.
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Rapid recruitment of macrophages in interleukin-12-mediated tumour regression. / Ha, Sang-Jun; Lee, S. B.; Kim, C. M.; Shin, H. S.; Sung, Y. C.

In: Immunology, Vol. 95, No. 1, 15.09.1998, p. 156-163.

Research output: Contribution to journalArticle

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