To compare the pulmonary toxicity between ultrafine colloidal silica particles (UFCSs) and fine colloidal silica particles (FCSs), mice were intratracheally instilled with 3 mg of 14 nm UFCSs and 230 nm FCSs and pathologically examined from 30 minutes to 24 hour postexposure. Histopathologically, lungs exposed to both sizes of particles showed bronchiolar degeneration and necrosis, neutrophilic inflammation in alveoli with alveolar type II cell swelling and particle-laden alveolar macrophage accumulation. UFCSs, however, induced extensive alveolar hemorrhage compared to FCSs from 30 minutes onwards. UFCSs also caused more severe bronchiolar epithelial cell necrosis and neutrophil influx in alveoli than FCSs at 12 and 24 hours postexposure. Laminin positive immunolabellings in basement membranes of bronchioles and alveoli of UFCSs treated animals was weaker than those of FCSs-treated animals in all observation times. Electron microscopy demonstrated UFCSs and FCSs on bronchiolar and alveolar wall surface as well as in the cytoplasm of alveolar epithelial cells, alveolar macrophages and neutrophils. Type I alveolar epithelial cell erosion with basement membrane damage in UFCSs treated animals was more severe than those in FCSs-treated animals. At 12 and 24 hours postexposure, bronchiolar epithelial cells in UFCSs-treated animals showed more intense vacuolation and necrosis compared to FCSs-treated animals. These findings suggest that UFCSs have greater ability to induce lung inflammation and tissue damages than FCSs.

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Only 10-15% of unseparated thymocytes adhered to culture plates precoated with fibronectin (FN), but 60-70% of the CD4-8-(double-negative) thymocyte population did. This population bound to FN but not to collagen, laminin, or vitronectin. Its binding to FN was inhibited by anti-FN antibody or a mixture of synthetic peptides corresponding to two different sites of EN, termed the V10 sequence and the RGDS (Arg-Gly-Asp-Ser) sequence, which interact, respectively, with the VLA-4 and VLA-5 FN receptors expressed on T-lineage cells. CD4-8-thymocytes also adhered to a monolayer of a thymic stromal cell clone, MRL104.8a, that induces growth-maintenance and differentiation of such thymocytes. . Most important, blocking the adhesion of CD4-8-thymocytes to the thymic stromal cell monolayer resulted in potent inhibition of the differentiation of these thymocytes, which was otherwise induced toward the expression of CD4 and/or CD8 molecules. These results indicate that immature CD4-8-thymocytes adhere to thymic stromal cells preferentially through FN-FN receptor interaction and that such adhesion has a critical role in inducing and/or supporting the differentiation of these thymocytes.Lymphocytes express a number of surface molecules that mediate the adhesion of cells to one another or to extracellular matrix (ECM) components (1-4). For example, cell-cell interaction molecules such as CD2 and LFA-3 are used to augment specific adhesion of T cells to antigen-presenting cells (5), and other cell-cell interaction molecules function as homing receptors (6, 7). Thus, these cell surface molecules have been recognized as regulating the migration of lymphocytes as well as the interactions of activated lymphocytes during immune responses.Another type of cell adhesion mechanism involves the interaction of cells with ECM (2, 4). While the importance of such cell-cell interactions in developmental biology has been documented (8-12), few studies have investigated the role of cell-ECM adhesion mechanisms in lymphocyte development in lymphopoietic microenvironments such as the bone marrow and thymus. This may be ascribed to the lack of in vitro systems for such analyses and to the complexity arising from the expression of various forms of ECM molecules regulated in a tissue-and cell-specific fashion, as exemplified by fibronectin (FN) molecules (13-15). In this context, several lines of marrow and thymic stromal cells have been isolated to provide tools for analyzing the interaction between developing lymphocytes and stromal cells (16). We have also established a thymic stromal cell clone that is capable of providing an in vitro model for intrathymic T-cell development (17-19).The present study investigates the role of FN molecules expressed on thymic stromal cells in thymocyte-stromal cell adhesion and thymocyte differentiation. The results demonstrate that CD4-8-("double-negative") thymocytes adhere to thymic stromal cells through FN molecules on the stromal cells. Molecular analyses revealed that two adhesion sites, the classic...

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