thymosin and Tuberculosis--Pulmonary

Recent studies have shown that thymosin β4 (Tβ4) stimulates angiogenesis by inducing vascular endothelial growth factor (VEGF) expression and stabilizing hypoxia inducible factor-1α (HIF-1α) protein. Pulmonary tuberculosis (TB), a type of granulomatous disease, is accompanied by intense angiogenesis and VEGF levels have been reported to be elevated in serum or tissue inflamed by pulmonary tuberculosis. We investigated the expression of Tβ4 in granulomatous lung tissues at various stages of active pulmonary tuberculosis, and we also examined the expression patterns of VEGF and HIF-1α to compare their Tβ4 expression patterns in patients' tissues and in the tissue microarray of TB patients. Tβ4 was highly expressed in both granulomas and surrounding lymphocytes in nascent granulomatous lung tissue, but was expressed only surrounding tissues of necrotic or caseous necrotic regions. The expression pattern of HIF-1α was similar to that of Tβ4. VEGF was expressed in both granulomas and blood vessels surrounding granulomas. The expression pattern of VEGF co-localized with CD31 (platelet endothelial cell adhesion molecule, PECAM-1), a blood endothelial cell marker, and partially co-localized with Tβ4. However, the expression of Tβ4 did not co-localize with alveolar macrophages. Stained alveolar macrophages were present surrounding regions of granuloma highly expressing Tβ4. We also analyzed mRNA expression in the sputum of 10 normal and 19 pulmonary TB patients. Expression of Tβ4 was significantly higher in patients with pulmonary tuberculosis than in normal controls. These data suggest that Tβ4 is highly expressed in granulomatous lung tissue with active pulmonary TB and is associated with HIF-1α- and VEGF-mediated inflammation and angiogenesis. Furthermore, the expression of Tβ4 in the sputum of pulmonary tuberculosis patients can be used as a potential marker for diagnosis.

Topics: Biomarkers; Fluorescent Antibody Technique; Granuloma, Respiratory Tract; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lung; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sputum; Thymosin; Tuberculosis, Pulmonary; Vascular Endothelial Growth Factor A

Topics: Adjuvants, Immunologic; Animals; B-Lymphocytes; Guinea Pigs; Lymphopenia; T-Lymphocytes; Thymosin; Thymus Extracts; Tuberculosis, Pulmonary

Specific pathogen-free, adult thymectomized, irradiated, and bone marrow-reconstituted (THXB) B6D2 mice were infected aerogenically with 1 X 10(3) to 5 X 10(3) live BCG Pasteur. Seven days later a group of the mice was placed on a 14-day regimen of 20 mg of calf thymosin per kg per day, and the growth of the BCG in the lungs, spleen, inguinal lymph node, bone marrow, and blood was determined for up to 90 days. The thymosin treatment was followed by a decline in the BCG counts for the lungs and spleens of the THXB mice, whereas the saline-treated controls showed no such decline with time. The thymosin-treated mice did not develop progressive BCG infections in the test lymph nodes or in the bone marrow, both of which became positive in the THXB mice. Spleen cells were harvested from thymosin-treated THXB donors, filtered through nylon wool, and infused three times into BCG-infected THXB recipients. The lung BCG counts declined approximately 10-fold by day 90 compared with THXB mice which received THXB spleen cells. The transferred immune response was only slightly smaller numerically than that seen in THXB mice infused with BCG-immune lymphocytes from normal donors.

Topics: Animals; BCG Vaccine; Blood; Bone Marrow; DNA; Immunity, Cellular; Immunity, Maternally-Acquired; Lymph Nodes; Mice; Mycobacterium bovis; Specific Pathogen-Free Organisms; Spleen; T-Lymphocytes; Thymosin; Thymus Hormones; Tuberculosis, Pulmonary

The percentage of E-rosette forming T-lymphocytes is considerably decreased in a number of patients with severe form of lung tuberculosis, particularly in those with tuberculous empyema of the pleura (28.5% to 38%). After in vitro incubation of lymphocytes from those patients with thymosin V fraction T-lymphocytes restored normal.

Topics: Adult; Empyema, Tuberculous; Humans; Male; Middle Aged; Rosette Formation; T-Lymphocytes; Thymosin; Thymus Hormones; Tuberculosis, Pulmonary