help button home button Am J Pathol Epitomics, Inc.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wynn, A. A.
Right arrow Articles by Takahashi, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wynn, A. A.
Right arrow Articles by Takahashi, K.
(American Journal of Pathology. 2001;158:131-145.)
© 2001 American Society for Investigative Pathology

Regular Articles

Role of Granulocyte/Macrophage Colony-Stimulating Factor in Zymocel-Induced Hepatic Granuloma Formation

Aye Aye Wynn*, Kazuhisa Miyakawa*, Emi Miyata*, Glenn Dranoff{dagger}, Motohiro Takeya* and Kiyoshi Takahashi*

From the Second Department of Pathology,*
Kumamoto University School of Medicine, Kumamoto, Japan; and the Department of Adult Oncology,{dagger}
Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts

To examine the role of granulocyte/macrophage colony-stimulating factor (GM-CSF) in inflammatory granuloma formation, we injected GM-CSF-deficient (GM-CSF-/-) mice and wild-type (GM-CSF+/+) mice intravenously with 2 mg of zymocel, and mice were killed at various intervals for examination. In GM-CSF-/- mice, we demonstrated a marked delay of zymocel-induced hepatic granuloma formation until 5 days after zymocel injection with a rapid reduction in numbers of granulomas at 10 days until their disappearance. In the early phase of granuloma formation, monocyte infiltration and differentiation of monocytes into macrophages were impaired in GM-CSF-/- mice compared with GM-CSF+/+ mice. The percentages of [3H]thymidine-labeled macrophages at 2 days after zymocel injection were lower in the GM-CSF-/- mice than in the GM-CSF+/+ mice. The DNA nick-end-labeling method demonstrated increased numbers of apoptotic cells in and around hepatic granulomas of GM-CSF-/- mice from 8 days after zymocel injection, and electron microscopy detected apoptotic bodies. Granuloma macrophage digestion of glucan particles and activation of macrophages were similar in the two types of mice. In situ hybridization demonstrated expression of GM-CSF mRNA in the endothelial cells, hepatocytes, and some granuloma cells in the GM-CSF+/+ mice but not in the GM-CSF-/- mice. These results provide evidence that GM-CSF is important for the influx of monocytes into hepatic granulomas, for differentiation of monocytes into macrophages, and for proliferation and survival of macrophages within hepatic granulomas.




This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
H. Nochi, N. Aoki, K. Oikawa, M. Yanai, Y. Takiyama, Y. Atsuta, H. Kobayashi, K. Sato, M. Tateno, T. Matsuno, et al.
Modulation of Hepatic Granulomatous Responses by Transgene Expression of DAP12 or TREM-1-Ig Molecules
Am. J. Pathol., April 1, 2003; 162(4): 1191 - 1201.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. W. O'REGAN, J. M. HAYDEN, S. BODY, L. LIAW, N. MULLIGAN, M. GOETSCHKES, and J. S. BERMAN
Abnormal Pulmonary Granuloma Formation in Osteopontin-deficient Mice
Am. J. Respir. Crit. Care Med., December 15, 2001; 164(12): 2243 - 2247.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2001 by the American Society for Investigative Pathology.