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Published on: December 11, 2015
Morphological aspects of giant cells in giant cell arteritis: an electron-microscopic and immunocytochemical study
E Nordborg1, B A Bengtsson, V Petursdottir
1Department of Rheumatology, Sahlgren's University Hospital, Göteborg, Sweden.
Insights
Giant cell arteritis (GCA) involves two distinct giant cell types with differing morphologies and distributions. These differences suggest unique functions and origins for foreign body giant cells and Langhans giant cells in GCA.
Area of Science:
- Vascular pathology
- Immunohistochemistry
- Cell biology
Background:
- Giant cell arteritis (GCA) is a systemic vasculitis characterized by inflammation of large and medium-sized arteries.
- Giant cells are a prominent feature in GCA, but their specific roles and origins are not fully understood.
Observation:
- Foreign body giant cells in GCA are associated with internal elastic membrane calcification in atrophic arterial segments.
- Langhans giant cells are found throughout the arterial wall in diffusely inflamed segments.
- Electron microscopy reveals distinct ultrastructural differences in lysosomes and cytoplasmic components between the two cell types.
Findings:
- Foreign body giant cells exhibit peripheral lysosomes and close association with calcified internal elastic membrane.
- Langhans giant cells show more central lysosomes and are found in all arterial wall layers during diffuse inflammation.
- Immunocytochemistry indicates differential expression of macrophage markers (KP1) and alpha-smooth muscle actin (alpha-SMA) between the two giant cell types.
Implications:
- The observed morphological and immunophenotypic differences suggest distinct functional roles and histogenetic origins for foreign body and Langhans giant cells in GCA.
- Further research into these cellular differences may reveal novel therapeutic targets for GCA.
Objectives:
To compare the morphology of foreign body and Langhans giant cells in the two different inflammatory phases of giant cell arteritis (GCA).
Methods:
Electron microscopy was performed on 6 positive temporal arterial biopsies. Light microscopy and immunocytochemistry for macrophage-associated antigen (KP1) and alpha-smooth muscle actin (alpha-SMA) were performed on 16 positive biopsies.
Results:
A focal granulomatous reaction with foreign body giant cells was found only in association with the internal elastic membrane (IEM) in atrophic arterial segments, which often displayed calcification of the IEM. Diffuse invasion of lymphocytes and monocytes/macrophages affected non-atrophic as well as atrophic arterial segments. Within such segments Langhans giant cells were found in all layers of the wall. Electron microscopy of biopsies displaying the focal foreign body reaction revealed that large cells devoid of lysosomes but with cytoplasmic densities, tightly packed cytoplasmic filaments and numerous micropinocytotic vesicles formed clusters close to calcified parts of the internal elastic membrane. Furthermore, foreign body giant cells were surrounded by large cells devoid of lysosomes. Lysosomes tended to concentrate in central parts of the foreign body giant cells. In the diffusely inflamed arteries, the Langhans giant cells were surrounded by mononuclear cells rich in lysosomes. The lysosomes in the Langhans giant cells were more evenly distributed than in foreign body giant cells. Immunocytochemistry of biopsies displaying the focal granulomatous reaction revealed an uneven, often central immunoreactivity for the macrophage marker (KP1) in the foreign body giant cells, and immunostaining for alpha-smooth muscle antigen (alpha-SMA) showed their poor delineation from the surrounding vascular smooth muscle cells. The Langhans giant cells in the diffusely inflamed arteries displayed a strong even cytoplasmic immunoreactivity for KP1 and a distinct delineation from the smooth muscle cells in the alpha-SMA staining.
Conclusion:
Differences in terms of distribution, light microscopy, immunocytochemistry and electron microscopy between the two types of giant cells in GCA indicate a difference in their function as well as their histogenesis.

