Enhanced production of TGF-beta by blood monocytes from patients with active tuberculosis and presence of TGF-beta in tuberculous granulomatous lung lesions.
The expression of TGF-beta, a molecule that affects both immune responsiveness and wound healing, was examined in blood monocytes and granulomatous lesions from patients with active pulmonary tuberculosis. The spontaneous release of TGF-beta was higher in culture supernatants of monocytes from patients as compared with those of healthy subjects by an ELISA (p < 0.0005). TGF-beta activity was also confirmed in a bioassay in supernatants from patients. Next, freshly isolated monocytes from patients with tuberculosis and matched subjects were examined for TGF-beta activity. Cytosmears of monocytes were stained with an Ab against TGF-beta 1 (anti-LC) or isotype-specific Ab by using an alkaline-phosphatase anti-alkaline phosphatase method. In contrast to monocytes from healthy individuals, 60 to 70% of monocytes from patients demonstrated cytoplasmic staining for TGF-beta (n = 3). Upon hypotonic lysis, monocytes from patients with tuberculosis contained immunoreactive TGF-beta (n = 3). By Northern blot analysis, monocytes from three of seven patients with tuberculosis had increased expression of TGF-beta mRNA as compared with concurrently examined monocytes from healthy subjects. Within the granulomas of lung sections from two patients with untreated tuberculosis, TGF-beta immunoreactivity was identified in the Langhan's giant cells mainly and to a lesser extent the epithelioid cells using anti-LC Ab and the peroxidase-anti-peroxidase technique. Thus, both blood monocytes and lung granuloma macrophages from patients with active tuberculosis express TGF-beta. Excess activity of this cytokine in blood monocytes may underlie the depressed T cell responses of patients with tuberculosis. Moreover, within the infected tissues excess TGF-beta activity may interfere with anti-mycobacterial mechanisms and effective granuloma formation.
Toossi
Z
Z
Department of Medicine, Case Western Reserve University, Cleveland, OH 44106.
Gogate
P
P
Shiratsuchi
H
H
Young
T
T
Ellner
J J
JJ
D015870:Gene Expression; D006801:Humans; D008168:Lung / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D014375:Tuberculoma / Q000378:metabolism*; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000276:immunology* / Q000473:pathology
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta