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Alveolar macrophages are the main source for tumour necrosis factor- in patients with sarcoidosis

¹ Dept of Internal Medicine (Respiratory Medicine), Philipps-University, Marburg, ² Dept of Pneumology, Medical University Hospital, Freiburg, ³ Dept of Clinical and Experimental Pathology, Medical Hospital, Research Centre, Borstel, and ⁴ Dept of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany

CORRESPONDENCE: H. Fehrenbach, Clinical Research Group "Chronic Airway Diseases", Dept. of Internal Medicine (Respiratory Medicine), Philipps-University, Baldingerstrasse, D-35034, Marburg, Germany. Fax: 49 64212868987. E-mail: heinz.fehrenbach@mailer.uni-marburg.de

Keywords: alveolar macrophages, granuloma formation, sarcoidosis, tumour necrosis factor

Received: September 4, 2002
Accepted November 25, 2002

This work was supported by a grant from the Deutsche Forschungsgemeinshaft (DFG, Mu692/5-6) and the Bundesministerium für Bildung und Forschung (BMBF, 01ZZ5904).

Tumour necrosis factor (TNF)- is known to play a major role in the formation of noncaseating granuloma, a hallmark of sarcoidosis. The main cellular source in situ is still ambiguous.

Serial sections of transbronchial biopsies from 14 patients with and 12 without sarcoidosis were studied, using immunohistochemistry (IHC), for TNF-, T-cells (CD3), macrophages (CD68), and epithelial cells (MNF116). TNF- spontaneously released (sr-TNF-) by freshly isolated bronchoalveolar lavage cells, isolated from the same patients and cultured without any stimulus over a 24-h period was measured using an enzyme-linked immunosorbent assay.

IHC revealed colocalisation of TNF- with CD68 cells only. Cases with TNF- tissue immunoreactivity exhibited higher sr-TNF- (1,667±504 pg·mL^–1) than cases without tissue immunoreactivity (211±60 pg·mL^–1). In an explorative approach, a subgroup of patients could be identified and characterised by the presence of alveolar macrophage aggregates. It was found that sr-TNF- was highest in this subgroup (2,700±769 pg·mL^–1) compared with patients with normal histology (221±61 pg·mL^–1) or with prominent granuloma (460±137 pg·mL^–1), whereas in most clinical parameters this subgroup was intermediate.

The findings from this study strongly corroborate the view that alveolar macrophages are the main cellular source for tumour necrosis factor- in the initial phase of sarcoidosis. The authors suggest that in these patients, aggregates of alveolar macrophages may represent at least predecessors to granulomas if not granulomas in statu nascendi.

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