Macrophages overloaded with tissue debris in Wegener’s granulomatosis
- 1Department of Pathology, Vilnius University Institute of Experimental and Clinical Medicine, Lithuania
- 2Laboratory of Rheumatology, The Finsen Centre, Rigshospitalet National University Hospital, Copenhagen, Denmark
- 3Department of Pathology, The Laboratory Centre, Rigshospitalet National University Hospital, Copenhagen, Denmark
- 4Department of Cell Biology, University of Opole, Poland
- 5III. Department of Internal Medicine of Palacky University, Olomouc, Czech Republic
- 6Department of Medicine/invärtes medicin, Helsinki University Central Hospital, Helsinki, ORTON Orthopaedic Hospital of the Invalid Foundation, Helsinki, and COXA Hospital for the Joint Replacement, Tampere, Finland
- Correspondence to:
Professor Y T Konttinen
Department of Medicine/invärtes medicin, PO Box 700 (Haartmaninkatu 8), FI-00029 Helsinki University Hospital, Helsinki, Finland;
- Accepted 30 January 2005
Objectives: To analyse some scavenging related molecules in Wegener’s granulomatosis (WG) macrophages.
Methods: Immunohistochemical staining of lung, nasopharynx, and skin for macrophage markers related to scavenging (macrophage scavenger receptor MARCO, collagenase-1 and gelatinase-B), formation of multinuclear foreign body giant cells (ADAM 9/meltrin-γ and ADAM 12/meltrin-α), and cell debris derived from neutrophils, endothelial cells and mast cells (specific granule protein 28 (SGP28), von Willebrand factor (vWF) and mast cell tryptase, respectively). TechMate staining robot and biotin-streptavidin protocol were used.
Results: Some macrophages were activated and expressed collagenase-1 and gelatinase-B. Approximately 5% of macrophages expressed scavenger receptor, whereas 20–30% were meltrin positive. Interstitial and granuloma associated macrophages and giant cells contained partly undigested, immunoreactive SGP28-, vWF- and tryptase-positive cell rests and collagenous matrix. Lymphocytic follicles with germinal centres were found in the same areas.
Conclusion: In WG tissue lesions macrophage and giant cells seem to be overwhelmed by the bulk to be scavenged. Despite cellular activation and continuing maturation to professional scavenger receptor (MARCO) and meltrin positive multinuclear giant cells combined with an organisation into granulomas, macrophages still contain partially undigested cell and tissue rests. This necrotic and damaged self may be the driving force for the formation of giant cell (“foreign body”) granulomas. This, together with the local formation of secondary lymphatic follicles (with germinal centres), indicates active local antigen processing and presentation.
- ADAM 9 and ADAM 12, transmembrane proteins of the zinc protease superfamily
- cANCA, antineutrophil cytoplasmic autoantibodies
- MARCO, macrophage scavenge receptor
- MCT, mast cell tryptase
- MMP, matrix metalloproteinase
- PR3, proteinase 3
- SGP28, specific granule protein
- vWF, von Willebrand factor
- WG, Wegener’s granulomatosis