Distribution and Presumed Proliferation of Macrophages in Inflammatory Diseases of the Ocular Adnexae

ABSTRACT

Purpose: The aim of this article is to investigate whether macrophages show a proliferative activity (as indicated by Ki67 expression) and their distribution at the site of inflammation.

Materials and Methods: Six different macrophage-containing lesions from six different patients (four females, two males; age range: 16–58 years) were stained for macrophage markers (CD68, CD163) and Ki67 by immunohistochemistry. Immunofluorescence techniques were used to investigate dual-labeling of the specimens for CD68, CD163 and Ki67, respectively.

Results: With immunofluorescence staining, scattered cells in all specimens were dual-labeled for CD68–Ki67 and CD163–Ki67. All lesions were composed of mixed infiltrates of M1 (CD68+CD163−) and M2 (CD68+CD163+) macrophages. The center of epithelioid-cell granulomas and foreign body giant cells was exclusively composed of M1 macrophages.

Conclusions: This study shows that CD68+ and CD163+ cells express Ki67, a marker for proliferative activity at the site of inflammation. Until recently, macrophages were regarded as end-differentiated cells without mitotic activity. Since self-renewal of M1 and M2 macrophages has been described in the literature, staining of macrophages with Ki67 may indicate proliferative activity or at least an activation state. The distribution of macrophages in classic granulomatous lesions with only M1 macrophages in the avascular center represents an immune response to foreign body material, whereas the proangiogenic M2 macrophages are located mostly in the surrounding inflammatory tissue and seem to be mandatory for the vascularization of the inflammatory tissue.

• Inflammation
• Ki67
• macrophages
• ocular adnexae
• proliferation

ACKNOWLEDGMENTS

The authors would like to thank Professor C. Kurts for critically reading the manuscript and Claudine Strack and Parand Widmar for technical assistance.

DECLARATION OF INTEREST

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

The study was presented in parts on the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO), 2011.

Supplementary material available online

Supplementary Figures 1–4.