Increased expression of apoptosis signalling receptors by alveolar macrophages in sarcoidosis

Abstract

The Fas receptor (FasR) and the tumour necrosis factor (TNF) receptor 55/60 kDa (TNFR1) are recognized as apoptosis signalling receptors. They are known to be expressed by lymphocytes in association with immune regulation and immunological disorders. This study aimed to investigate the expression of FasR and TNFR1 by alveolar macrophages (AM) in patients with sarcoidosis. Bronchoalveolar lavage (BAL) was performed in 12 patients with active sarcoidosis and 11 control subjects. BAL cells were characterized by monoclonal antibodies using a peroxidase-antiperoxidase method. Both FasR and TNFR1 were expressed on a higher percentage of AM in sarcoidosis with respect to control subjects (mean +/-sem 40.8+/-3.1% versus 14.9+/-1.7%, p<0.001 and 61.9+/-3.3% versus 23.1+/-4.1%, p<0.001, respectively). There was a close relationship between the expression of FasR and TNFR1 on AM (r = 0.86, p<0.001). The percentages of FasR+ AM and TNFR1+ AM were in direct proportion to the percentage of BAL lymphocytes (r = 0.75 and 0.84), the CD4/CD8 ratio (r = 0.78 and 0.78), and the percentage of the CD14+ AM subset (r = 0.77 and 0.87), p<0.001 for all correlations. This study indicates that alveolar macrophages expressing apoptotic receptors are increased in patients with active sarcoidosis. Further studies are required to determine whether these alveolar macrophages from patients with sarcoidosis undergo apoptosis more readily than those from control subjects.

Expression of tumour necrosis factor receptors by bronchoalveolar cells in hypersensitivity pneumonitis

“…This was discussed as a possible mechanism for the lymphopenia observed in SLE [5,16]. FasR can also be expressed on AM in sarcoidosis [6] and on human blood eosinophils [11]. In the present study, it was demonstrated that the expression of TNFR-1 closely correlated with the expression of TNFR-2 on AM, and that both receptors correlated with the percentage of lymphocytes, and inversely with the percentage of macrophages in the BAL of HP patients.…”

“…A previous study from the current authors revealed an increased expression of TNFR-1 and FasR on BAL macrophages of patients with sarcoidosis, which is another granulomatous lung disease [6]. The expression of TNFR-2 and FasR has been reported to be increased on BAL lymphocytes in sarcoidosis and HP [5].…”

“…In contrast, expression of TNFR-1 was not observed on BAL lymphocytes in both diseases, and only minor expression was reported on blood lymphocytes in HP [5]. The expression of TNFR-1 and FasR on BAL macrophages was noted to be increased in sarcoidosis [6]. These two receptors were found to be upregulated on synovial tissue cells in rheumatoid arthritis compared with peripheral blood mononuclear cells (PBMC) [15].…”

“…These receptors can lead to either apoptosis or survival of immune cells when ligated by their corresponding ligands [4]. Some studies have shown the involvement of apoptotic receptors in interstitial lung diseases [5,6].…”

Elimination of lymphocytes, but not eosinophils, by Fas-mediated apoptosis in murine schistosomiasis.

“…For example, apoptosis has been demonstrated in the granulomas associated with schistosomiasis, 9,16 sarcoidosis, 21,22 and other infectious diseases such as Propionibacterium acnes, leprosy, tuberculosis, and hepatitis. [21][22][23][24][25] Eosinophils have been shown to undergo Fas-mediated apoptosis in some systems. In a study by deAndres and others, when hepatic granulomas of S. mansoni-infected mice were cultured in the presence of anti-Fc␥RIII antibody, the eosinophils underwent Fas-dependent apoptosis within 24 hr.…”