concanavalin-a and Silicosis

In chronic silicosis, mechanisms leading to lymphocyte activation are still poorly understood, although it is well known that not only the lung but also the draining lymph nodes are affected. In the present study, we investigated T-cell activation by analysis of cytokine expression in the enlarged thoracic lymph nodes of rats 2 mo after an 8-day silica aerosol exposure. In the case of helper T cell (Th) type 1 cytokines, we found a significant increase in interferon (IFN)-gamma mRNA expression, whereas interleukin (IL)-2 expression remained unchanged. In contrast, gene transcription for the Th2-type cytokines IL-4 and IL-10 was diminished. In addition, with use of an in vitro lymphocyte-macrophage coculture system, an enhanced IFN-gamma and a reduced IL-10 release were shown with cells from silicotic animals. With regard to IFN-gamma-inducing cytokines, we observed enhanced IL-12 mRNA levels in vivo, whereas IL-18 gene expression was slightly decreased. These data indicate that a persistent shift toward an IFN-gamma-dominated type 1 (Th1/cytotoxic T cell type 1) T-cell reaction pattern occurred within the thoracic lymph nodes of silicotic animals. Thus a mutual activation of lymphocytes and macrophages may maintain the chronic inflammatory changes that characterize silicosis.

Topics: Animals; Coculture Techniques; Concanavalin A; Cytokines; Gene Expression; Interferon-gamma; Interleukin-12; Interleukin-18; Lymph Nodes; Lymphocyte Activation; Macrophages; Male; Rats; Rats, Inbred F344; RNA, Messenger; Silicosis; Th1 Cells; Th2 Cells; Thorax

In order to study changes in lung histology and lymphocyte function during the development of pneumoconiosis, three groups of Balb/c mice were intratracheally instilled with either saline, chrysotile asbestos or silica particles and then sacrificed at different times. Asbestos-instilled mice showed collagen deposits at 2 months while silica-instilled mice showed severe fibrosis at that time. Stimulation of splenic cells with LPS was not affected by instillation of the toxic particles. Stimulation with PHA and ConA, however, induced increased responses especially at 3 and 6 months after instillation of asbestos or silica. A diminution of mitogen-induced proliferation was observed in aged mice. There was no correlation between changes in splenic cell proliferation and development of fibrosis. Asbestos fibers added in vitro, inhibited PHA and ConA-induced proliferation, partially due to prostaglandin (PG) production and to the presence of the fibers during the assay. When asbestos fibers were removed by washing, no inhibition was observed. Moreover, actual stimulation of proliferation was noted when PG production was inhibited in vitro with indomethacin. In contrast, in vivo treatment of asbestos-instilled mice with indomethacin had no effect on the development of lung pathology.

Topics: Animals; Asbestosis; Cell Adhesion; Concanavalin A; Indicators and Reagents; Lipopolysaccharides; Lung; Lymphocytes; Male; Mice; Mice, Inbred BALB C; Phytohemagglutinins; Pulmonary Fibrosis; Silicosis; Spleen

The function of lymphocytes and monocytes was compared in a group of 18 ex-sandblasters with silicosis and 19 control subjects. Previously noted depressed lymphocytic proliferation in response to low concentrations of concanavalin A (ConA) in subjects with silicosis was not due to factors in the serum nor correctable by supplementation with allogeneic lymphocytes. Monocytes from the peripheral blood of the subjects with silicosis responded less to a chemotactic stimulus (zymosan-activated serum) than did monocytes from normal laboratory personnel; however, there was no difference in monocytic chemotaxis when groups of similar age were compared. There was a significant correlation between age and the monocytic response to chemotactic stimuli in the studied population (laboratory personnel, silicotic subjects, and age-matched control subjects). Overall, our data suggest subtle effects of silica on selected T-lymphocytic populations involved with responsiveness to the mitogen, concanavalin A, but no effects on monocytic function. Monocytic chemotaxis is unaffected by exposure to silica but is inversely related to age.

Topics: Age Factors; Cell Division; Chemotaxis; Concanavalin A; Humans; Infections; Middle Aged; Mitogens; Monocytes; Silicosis; T-Lymphocytes