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L Paglia

Publications and source records attributed to L Paglia.

At least 19 recordsLinked to original sources
PubMed1986

Bacterial cell wall-induced hepatic granulomas. An in vivo model of T cell-dependent fibrosis.

In vitro studies implicate a molecular link between inflammatory mononuclear cells and alterations in fibroblast growth and function. We have extended these observations in an experimental animal model in which we document the T cell-dependence of fibrosis that occurs after activation of the cell-mediated immune system by specific antigen. Chronic granulomatous lesions were induced in the livers of susceptible rats by the intraperitoneal injection of group A streptococcal cell walls (SCW). The development of granulomas that are composed primarily of lymphocytes and macrophages was associated with the recruitment and proliferation of connective tissue cells. Furthermore, this expanded population of fibroblasts generated a collagenous structure consisting primarily of types I and III collagen around the granuloma. The progression of these chronic inflammatory lesions leads to the formation of fibrotic nodules throughout the livers of the treated animals. Intact granulomas, as well as mononuclear cells derived from the granulomas, spontaneously elaborated a soluble factor(s) that stimulates fibroblast proliferation. Physicochemical analysis revealed that the primary granuloma-derived peak of fibroblast growth activity corresponded to an apparent Mr of 40,000, which is consistent with a previously described T lymphocyte--derived fibroblast-activating factor (FAF) in guinea pig and human. Furthermore, the fibrosis that occurs in the granuloma is apparently T cell--dependent, since no fibrotic lesions developed in SCW-injected athymic nude rats nor in SCW-injected animals treated with the T cell inhibitor, cyclosporin A (CsA). Mononuclear cells from neither of these functionally T cell--deficient animals could generate FAF activity. These data show a role for T lymphocyte--derived cytokines in the development of hepatic fibrosis in SCW-injected rats.

Animals↗
PubMed1985

Chemoattractants in fibrotic disorders.

Fibrosis represents an excessive deposition of connective tissue which impedes the normal functions of an organ or tissue. The mechanisms leading to this increased deposition of connective tissue may be similar to those occurring in normal wound repair. We have previously shown that the repair process involves the migration of connective tissue cells to the site of injury and their subsequent proliferation. One of the principal factors controlling these events appears to be the platelet-derived growth factor (PDGF). PDGF acts as a potent chemoattractant and mitogen for connective tissue cells but not other cell types. In addition to PDGF, factors produced by monocytes and tissue macrophages also act as chemoattractants for connective tissue cells. These observations suggest that such activities may be abundant in areas of inflammation. In normal repair these factors would be present for a relatively short period of time, whereas in fibrosis the chronic inflammatory response could maintain a constant or repeated release of such factors. This would recruit additional connective tissue cells to the area of inflammation, changing the cellular composition of the affected organ or tissue, resulting in an expansive and permanent nodule of connective tissue.

Animals↗
PubMed1981

Isolation and partial characterization of active polysomes from calcified and matrix-containing tissues.

Polysomes were isolated from calcified and matrix-containing tissues, such as rat calvaria, rat chondrosarcoma and chick embryos. The method of isolation involves preliminary swelling of the tissues in hypotonic buffer containing heparin and cycloheximide. After homogenization, differential centrifugation is used to separate membrane-bound and non-bound polysomes. Each fraction is rehomogenized in the presence of detergent (Triton X-100) and potassium ions (0.25M). Polysomes are harvested by centrifugation through sucrose cushions in the continued presence of high levels of potassium ions and heparin. Total, non-bound, and membrane-bound polysomes prepared in this manner are equally active in protein synthesizing activity in an heterologous cell-free system. The distribution between non-bound and membrane-bound polysomes in the 12 day old chick embryo is 43 and 57 per cent respectively. Sucrose gradient profiles of polypeptide chains on polysomes labeled in organ culture correlate well with the protein synthetic activity of the isolated polysomes. Much of the protein synthetic activity is devoted to collagen. Polysomal fractions obtained from sucrose gradients show preferential incorporation of 3H-proline and nearly 60 per cent of trichloroacetic acid precipitable material is susceptible to collagenase digestion. Products of synthesis are also substrates for collagen specific enzyme, prolyl hydroxylase. The method described in this communication overcomes the inherent difficulties in obtaining active polysomes from calcified and matrix-containing tissues.

Animals↗
PubMed1980

Partial characterization of procollagen messenger ribonucleic acid in a murine chondrosarcoma.

Cells from a rat chondrosarcoma in primary suspension culture were used for labeling studies and isolation of RNA. With extended labeling, a distinct fraction of poly(A+)RNA sedimented in the region of 26S on denaturing sucrose gradients. Similar profiles were obtained with labeled poly(A+)RNA isolated from normal cartilage tissues, as well as from chondrocytes in culture. This mRNA coded for collagenous protein when translated in a cell-free system derived from wheat germ. Among the polypeptides synthesized in vitro, one distinctive component of approximately 150,000 daltons was detected by gel electrophoresis. Polypeptides of identical size, sensitive to bacterial collagenase, were also synthesized in vitro by polysomes isolated from the chondrosarcoma.

Animals↗
PubMed1980

Synthesis of fibronectin, laminin, and several collagens by a liver-derived epithelial line.

We have investigated the ability of ARL-6 cells, a cell line derived from rat liver, to synthesize various collagens and two glycoproteins of the extracellular matrix, fibronectin, and laminin. Using immunofluorescence, we detected types I, II, and IV collagen plus laminin and fibronectin. Antibodies to types I and III collagen and to fibronectin were associated with most cells and showed a similar distribution. Type IV collagen and laminin were found in thin filaments associated with a small proportion of the cells. Chemical studies showed that ARL-6 cells synthesize predominantly types I and III collagens. The level of collagen synthesis was greatly affected by the presence of exogenous fibronectin added to the cells in the media. Cells maintained in fibronectin-free serum synthesized much less collagen. These studies indicate that liver-derived cells can synthesize a variety of connective tissue proteins and that collagen synthesis by these cells is enhanced by the presence of fibronectin.

Animals↗