Detection of tumour necrosis factor alpha in sarcoidosis and tuberculosis granulomas using in situ hybridisation.

Abstract

Aims-To determine the site of tumour necrosis factor a (TNFa) product and mRNA in granulomas. Method-In situ hybridisation with digoxigenin labelled or biotinylated oligonucleotide probes was used to demonstrate the presence of total mRNA, and then the presence of TNFa mRNA in the biopsy specimens of 37 granulomas (31 sarcoidosis, six tuberculosis). Results-TNFa mRNA was detected in epithelioid cells, giant cells, and lymphocytes in the granulomas. Some sarcoidosis specimens did not contain detectable mRNA for TNF, but did contain TNF peptide in the epithelioid or giant cells on immunostaining. This may have been due to stored TNF present in cells in which mRNA for TNF is no longer being produced. Conclusion-The results suggest that giant cells should not be regarded as effete cells, as they contain large amounts ofmRNA and seem to be actively producing TNFa. (7 Clin Pathol 1994;47:423-426)

The role of macrophage cell death in tuberculosis

“…Furthermore, Mancino et al (unpublished observations) found that in similar sections, typical tuberculous granulomata characterized by a core of caseous necrosis containing dying cells were surrounded by a cuff of apoptotic MF. The demonstration of increased TNF-a expression in these lesions 16 is consistent with its proposed role in macrophage apoptosis. The direct induction of macrophage apoptosis by M. tuberculosis is certainly only one of several pathways responsible for the TUNEL-positive cells demonstrated in clinical specimens.…”

“…Among them, tumor necrosis factor-a (TNF-a) is thought to play an important role and its expression in tuberculous granulomas has been directly demonstrated. 16 Antibody neutralization experiments, and studies of mice with targeted deletion of the TNF receptor p55 (TNFR1; 17) indicate that TNF-a is required for protection of the host. In the absence of TNF-R1, survival was dramatically reduced following infection with virulent M. tuberculosis and while granulomas formed in these animals, they contained more bacilli than controls and epithelioid cells were absent.…”

Reduced Th1 response in the lungs of HLA-DRB1*0301 patients with pulmonary sarcoidosis

“…As with previous studies on pulmonary sarcoidosis that demonstrated elevated expression of Th1 cytokines IL-2 and IFN-c, and showed little or no detectable expression of Th2 cytokines in BAL cells [3,24], these results are in line with a preferential Th1 cytokine expression at sites of disease in sarcoidosis. No significant changes in the transcript levels for TNF-a or IL-12p40 were found in BAL cells from sarcoidosis patients, which contrasted with some previous studies [24,25] but was in line with others [4,7,26,27]. Such discrepancies can depend on the choice of patient group, including smoking habits or previous/ongoing treatment, and the sensitivity of the methods.…”

Epithelioid Cell: A New Opinion on Its Nature, Parentage, Histogenesis, Cytomorphogenesis, Morphofunctional Potency, Role in Pathogenesis and Morphogenesis of Tuberculous Process

“…ECs-granulomas or the separate clumps of ECs will be derivated in many infectious diseases, including in tuberculosis (Malik et al, 1999;Russell et al,2009;Shkurupy, 2007), some rheumatic (Chadarevian et al, 1993), autoimmune (Ren, 1992), lymphoproliferative diseases (Takeshita et al, 1993), histiocytoses (Goerdt et al, 1993), in development of tumors of a different histogenesis (McCartney, 1995), granulomatous diseases of a unknown etiology (Kaneishi et al, 1995;Tozman, 1991), hit in an organism of salts of some metals (Haley et al, 1994;Kelly, 1993), foreign bodies (McCarthy et al, 1993), allergens of a different nature (Yamanaka et al, 1994). The issue of granulomatous process largely depends on dynamics of epithelioid-cell-like cytomorphosis in the centers of an inflammation that apparently is specified by morphofunctional features of ECs, permitting by it to fulfill simultaneously functions of boundary conditions (Hasegawa et al, 1994;Noga et al, 1989), exocellular damage of pathogen agents by products of secretion (Baba et al, 1992;Myatt et al, 1994;Tanaka et al, 1996), modulation of Mphs function activity (Mariano, 1995;Miyazaki et al, 1992;Shigenaga et al, 1995), lymphocytes (Abe et al, 1990;Chensue et al, 1992) and fibroblasts (Allen, 1991;Limper et al, 1994). Now is generally acknowledged that ECs are transformed from Mphs in an organ or tissue, where pathological granulomatous process is developed (Dastur et al, 1995;Moraes & Moraes, 1993;Russell, 2009;Takahashi et al, 1994), and under certain conditions -from monocytes of a blood (Facchetti et al, 1989;Williams & Williams, 1983).…”

“…It is fixed that the angiotensin converting enzyme can brake migration Mphs, that is play a role of the factor inhibiting migration of Mphs, that is important for formation of cell-like aggregate in granulomagenerating process (Mariano, 1995;Williams & Williams, 1983;). At usage enzyme-linked immunoassay methods it is exhibited that ECs produce IL-1, IL-2, IL-4, IL-6, TNF-(tumors necrosis factor), multifunctional growth factor TGF- (Limper et al, 1994;Myatt et al, 1994;Toossi et al, 1995). These data specify that ECs play important regulatory function in formation of granulomas and in pathogenesis of granulomatous diseases.…”