Tumour necrosis factor-alpha production in fibrosing alveolitis is macrophage subset specific

Deirdre McGrath, Panos Pantelidis, Anne Marie Southcott, Carol M. Black, Roland M. Du Bois

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Background: Previous studies have revealed that tumour necrosis factor (TNF)-α is upregulated in fibrosing alveolitis (FA) in humans. The aim of this study was to compare the TNF-α secretory profile of alveolar macrophages (AMs) and peripheral blood monocytes (Mos) of patients with cryptogenic FA and systemic sclerosis (SSc), a rheumatological disorder in which lung fibrosis can occur. In particular, we wished to assess whether TNF-α levels differ between SSc patients with FA (FASSc) and a nonfibrotic group. Methods: The reverse haemolytic plaque assay was used to evaluate the secretion of cytokine at a single cell level while immunostaining allowed subtyping of AMs and Mos. Results: This study demonstrated a difference in total TNF-α levels produced by AMs when the levels in subjects with FA (cryptogenic FA and FASSc) were compared to levels in either SSc patients without FA (P=0.0002) or normal healthy controls (P<0.001). In addition, AMs from patients with FASSc secreted more TNF-α than those of patients with no FA (P=0.003). In contrast, there were no significant differences in Mo TNF-α secretion between the groups. A positive correlation was found between total TNF-α level and number of neutrophils obtained by bronchoalveolar lavage from patients with FA (r=0.49, P<0.04). Finally, it was demonstrated that there was significant heterogeneity of TNF-α secretion and that a numerically significant subset of mononuclear phagocytes, RFD7, was responsible for more than 80% of TNF-α production. Conclusion: By demonstrating the primary cell source of TNF-α in FASSc, more accurately targeted, possibly localized, anti-TNF strategies might be employed with success in the future.

    Original languageEnglish (Ireland)
    Pages (from-to)365-372
    Number of pages8
    JournalRespiratory Research
    Volume2
    Issue number6
    DOIs
    Publication statusPublished - 2001

    Keywords

    • Fibrosing alveolitis
    • Haemolytic plaque
    • Macrophages
    • Monocytes
    • Systemic sclerosis
    • Tumour necrosis factor (TNF)-α

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