Am. J. Respir. Cell Mol. Biol.,
Volume 23, Number 3, September, 2000 313-319
Transcription of krox-20/egr-2 Is Upregulated after Exposure to Fibrous
Particles and Adhesion in Rat Alveolar Macrophages
Seishiro
Hirano,
C. D.
Anuradha,
and
Sanae
Kanno
Regional Environment Division, National Institute for Environmental Studies, Ibaraki, Japan
Alveolar macrophages meet various types of particulate substances deposited deep in the lung. We report differences in
biologic responses of alveolar macrophages between phagocytosis of fine spherical and fibrous particles. Although titanium dioxide (TiO2) is thought to be biologically inert, the
cytotoxicity of fibrous TiO2 (F-TiO2) was much higher than
spherical TiO2 (S-TiO2). Differential display and the subsequent Northern blot analysis indicated that transcription of
krox-20/egr-2 gene was slightly and greatly upregulated in S-
and F-TiO2-exposed alveolar macrophages, respectively. The messenger RNA (mRNA) level of krox-20/egr-2 increased up to
8 h in F-TiO2-exposed alveolar macrophages, whereas krox-20/egr-2 mRNA level was transiently increased in response to
adhesion to the culture dish. Stimulation with lipopolysaccharide also increased krox-20/egr-2 mRNA level transiently, although the mRNA level rebounded after 8 h. The analysis with
5' rapid amplification of complementary DNA ends suggested
that there is a heterogeneity in the upstream region of this
gene (krox-20/egr-2 and krox-20H1; accession numbers AB032420
and AB032419, respectively). The polymerase chain reaction
analysis with specific primers for krox-20/egr-2 and krox-20H1
indicated that both genes were almost equally upregulated
after either adhesion to the plastic dish or phagocytosis of
F-TiO2. These results suggest that both krox-20/egr-2 and krox-20H1 are implicated in adhesion and phagocytosis, and that
the expression of krox-20 may reflect interaction with foreign substances and adhesion in alveolar macrophages.