Activation and apoptosis of macrophages in cat scratch disease.
Cat scratch disease is an infectious disease usually caused by Bartonella henselae. Within 1-3 weeks after inoculation, patients typically develop regional self-limited lymphadenopathy. Lymph nodes reveal granulomas consisting of central necrosis, an inner rim of palisading macrophages, and an outer rim of lymphocytes and non-palisading macrophages. In animals, cat-scratch disease leads to an interferon-gamma (IFNgamma)-mediated T-helper 1 immune response, resulting in macrophage recruitment, stimulation, and thereby granuloma formation. The present study has sought to find in situ evidence for macrophage migration, activation, and cell death in human cat scratch disease. By non-radioactive in situ hybridization and immunohistochemistry on serial sections, it was demonstrated that IFNgamma+ T lymphocytes and S100A8+, S100A9+ macrophages embrace granulomas, which consisted of S100A8-, S100A9-, HLA-DR+, CD40+, TNFalpha+ macrophages. Combination of in situ end-labelling and immunofluorescence revealed large numbers of DNA-fragmented CD68+ cells with intact plasma membranes corresponding to apoptotic macrophages. On the basis of these data, it was hypothesized that in human cat scratch disease, S100A8+, S100A9+ macrophages continuously migrate to the granulomas. During this process, they may be activated by IFNgamma T-helper 1 lymphocytes and be differentiated to S100A8-, S100A9-sessile, HLA-DR+, CD40+ antigen-presenting, TNFalpha+ pro-inflammatory macrophages forming granulomas. In parallel, macrophages undergo apoptosis in the centre of granulomata, a phenomenon that may restrict the destructive potential of macrophages and contribute to self-limitation of cat scratch disease.
Schweyer
S
S
Department of Pathology, University of Göttingen, Göttingen, Germany. sswyer@med.uni-goettingen.de
Fayyazi
A
A
D017209:Apoptosis / Q000276:immunology*; D002372:Cat-Scratch Disease / Q000276:immunology* / Q000473:pathology; D006099:Granuloma / Q000276:immunology / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000276:immunology; D008198:Lymph Nodes / Q000473:pathology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D009336:Necrosis
D007371:Interferon-gamma