Macrophage infiltration and heme oxygenase-1 expression correlate with angiogenesis in human gliomas

Akihiro Nishie, Mayumi Ono, Tadahisa Shono, Junichi Fukushi, Michihiro Otsubo, Hitoshi Onoue, Yushi Ito, Takanori Inamura, Kiyonobu Ikezaki, Masashi Fukui, Toru Iwaki, Michihiko Kuwano

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302 Citations (Scopus)


Macrophages are key participants in angiogenesis. In this study on human brain tumors, we first investigated whether macrophage infiltration is associated with angiogenesis and malignant histological appearance. Immunostaining of macrophages and small vessels in resected glioma specimens indicated that numbers of infiltrating macrophages and small vessel density were higher in glioblastomas than in astrocytomas or anaplastic astrocytomas. Macrophage infiltration was closely correlated with vascular density in human gliomas. Heme oxygenase-1 (HO-1), which is the rate-limiting enzyme in heme catabolism, was also associated with activated macrophages. Expression of mRNA encoding HO-1 was correlated with macrophage infiltration and vascular density in human glioma samples. Infiltrating macrophages were positively stained with anti-HO-1 antibody by immunohistochemical analysis, and in situ hybridization for HO-1 indicated that HO-1 was expressed in infiltrating macrophages in gliomas. HO-1 gene may be a useful marker for macrophage infiltration as well as neovascularization in human gliomas.

Original languageEnglish
Pages (from-to)1107-1113
Number of pages7
JournalClinical Cancer Research
Issue number5
Publication statusPublished - May 1999

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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