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M Salmi

Publications and source records attributed to M Salmi.

72 records · Page 4Linked to original sources
PubMed1993

Endothelial cell-binding properties of lymphocytes infiltrated into human diabetic pancreas. Implications for pathogenesis of IDDM.

In IDDM, mononuclear cells accumulate in the islets of Langerhans and destroy insulin-producing beta-cells. To study the mechanisms that control extravasation of circulating mononuclear cells into the pancreas, we examined the phenotype of vascular endothelium of the pancreas, propagated a T-cell line from pancreatic islets at the onset of the disease and compared endothelial binding of this cell line in vitro to vascular endothelium in different body regions. The adhesion molecules expressed on the resulting T-cell line and the functional binding capacity of these cells to the endothelium of the normal and diabetic pancreas, mucosa-associated lymphatic tissues, and regional and peripheral lymph nodes were studied. We present evidence of pancreatic endothelial activation in diabetes, leading to endothelial morphology typical for HEVs and accompanying local increase in extravasation of mononuclear cells into the pancreas. Endothelial-cell binding experiments with the T-cell line showed strong adherence of the cells to the endothelium of diabetic pancreas and mucosal lymphoid tissue. The cell line was uniformly CD4-positive, TCR V beta 5.1-positive, LFA-1-positive (CD 11a/CD18), VLA-4 alpha-positive (CD 49d), and CD 44-positive but negative for L-selectin (peripheral lymph node homing receptor). The pancreatic or control cell lines showed no binding to vessels of normal pancreas, and the binding of the pancreatic cell line to the endothelium of peripheral lymph node was weak. Our results suggest that lymphocyte-endothelial cell interactions are important for the accumulation of inflammatory mononuclear cells into the pancreas and imply that lymphocytes derived from the mucosal lymphoid tissue may be involved in the pathogenesis of IDDM.

Cell Adhesion↗
PubMed1993

A novel endothelial cell molecule mediating lymphocyte binding in humans.

Leukocyte extravasation is critically dependent on proper interactions between leukocytes and vascular endothelial cells. Although several molecules mediating these interactions have been identified, all the homing phenomena observed in vivo cannot be explained on the basis of the known adhesion molecules. To discover novel molecules involved in leukocyte migration we have made monoclonal antibodies against human endothelial cells. With the help of one such monoclonal antibody a novel endothelial cell molecule called vascular adhesion protein-1 (VAP-1) was found. Uniqueness of VAP-1 is evident on the basis of its expression pattern, molecular mass, functional properties and N-terminal amino acid sequence. VAP-1 mediates lymphocyte binding to endothelium in peripheral lymph nodes, tonsil and inflamed synovium. Therefore, VAP-1 is relevant to understanding of the physiologic and pathologic lymphocyte migration in man, and may be valuable for dissecting the molecular events of tissue-selective lymphocyte homing.

Amine Oxidase (Copper-Containing)↗
PubMed1992

Selective endothelial binding of interleukin-2-dependent human T-cell lines derived from different tissues.

The ability of lymphocytes to recognize and bind to high endothelial venules (HEVs) is essential for lymphocyte migration from the blood into lymphoid tissues and into sites of inflammation. Endothelial cell binding capacity also critically determines the clinical usefulness of T-cell lines and clones in immunotherapy. In the present study, interleukin-2-dependent T-cell lines were derived from the blood, lamina propria of the gut, inflamed synovium, synovial fluid, and peripheral lymph nodes. After 3-8 weeks of culture, the expression of homing-associated molecules and binding to mucosal, synovial, and peripheral lymph node HEVs were analyzed. Cell lines derived from the blood and mucosal sites bound significantly better to mucosal and synovial HEVs than to peripheral lymph node HEVs. Three out of seven synovial T-cell lines showed preferential binding to synovial HEVs, whereas the rest bound almost equally well to synovial and mucosal HEVs. T-cell lines from peripheral lymph nodes bound preferentially to lymph node HEVs despite the lack of L-selectin (the peripheral lymph node homing receptor). Expression of the known homing-associated molecules did not predict the HEV-binding specificity of these lines. Importantly, two cell lines bound well to synovial venules, but poorly, if at all, to mucosal or peripheral lymph node HEVs, supporting the concept that synovial-specific HEV recognition mechanisms exist. In conclusion, the tissue origin of T-cell lines critically determines their selectivity for endothelial cell recognition, and besides the known "homing receptors," other molecules may also mediate tissue-specific HEV-binding of interleukin-2-activated T cells.

Antigens, CD↗
PubMed1992

A 90-kilodalton endothelial cell molecule mediating lymphocyte binding in humans.

Interactions between leukocyte surface receptors and their ligands on vascular endothelial cells control lymphocyte traffic between the blood and various lymphoid organs, as well as extravasation of leukocytes into sites of inflammation. A heretofore undescribed 90-kilodalton human endothelial cell adhesion molecule (VAP-1) defined by a monoclonal antibody 1B2 is described. The expression pattern, molecular mass, functional properties, and an amino-terminal amino acid sequence define VAP-1 as an endothelial ligand for lymphocytes. VAP-1 helps to elucidate the complex heterotypic cell interactions that direct tissue-selective lymphocyte migration in man.

Amine Oxidase (Copper-Containing)↗
PubMed1992

Regulation of L-selectin expression on cultured bone marrow leukocytes and their precursors.

L-selectin (LECAM-1, LAM-1, MEL-14 antigen, Dreg antigen) is one of the molecules controlling lymphocyte homing from the blood to peripheral lymph nodes and granulocyte adhesion to inflamed endothelium. In this work, regulation of L-selectin expression on mouse bone marrow cells was studied. L-selectin-negative cells were isolated by panning technique, cultured for 1-7 days with cytokines and mitogens, and L-selectin expression was analyzed by immunofluorescence staining. When cultured for 3 days with interleukin (IL) 1, IL 2, IL 5, IL 6, phytohemagglutinin, pokeweed mitogen or in the medium alone, 75%-85% of L-selectin-negative large cells (including granulocytes, macrophages/monocytes, blasts and their precursors) became L-selectin positive. In contrast, IL 3, IL 4, granulocyte-macrophage colony-stimulating factor (GM-CSF) and lipopolysaccharide (LPS) prevented the induction of L-selectin in a time- and dose-dependent manner. GM-CSF was the most potent inhibitor and only 10%-15% of cells became L-selectin positive after 3 days of culture. Furthermore, L-selectin was down-regulated on cultured unselected bone marrow cells by IL 3, IL 4, GM-CSF and LPS stimulation. After culture, the relative molecular mass of L-selectin was 100 kDa, similar to the size of the granulocyte form of this antigen. Cultured cells adhered to high endothelial venules (HEV) only 10%-32% as effectively as freshly isolated bone marrow cells despite high levels of L-selectin expression. The phenotypic analysis and the HEV binding data indicate that after culturing L-selectin was almost exclusively expressed on bone marrow leukocytes of myeloid series, and on these cells it was not functional in mediating peripheral lymph node HEV binding. Overall, these results show that the expression of L-selectin can be modulated by regulating the maturation and differentiation of the cells in vitro. This supports the idea that different cytokines and mitogens may also be important in controlling migrational status of leukocytes in vivo.

Animals↗
PubMed1992

Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulin-dependent diabetes mellitus.

Current knowledge of the phenotype of mononuclear cells accumulating in pancreatic islets in insulin-dependent diabetes (IDDM) and factors determining their homing into the pancreas is limited. Therefore, a pancreas obtained at the onset of IDDM was studied in detail. Cryostat sections were stained for mononuclear cell types, T cell receptor subtypes, and adhesion molecules of vascular endothelium and studied by immunofluorescence microscopy, and peripheral blood mononuclear cells were phenotyped using flow cytometry. Monocytes/macrophages (lysozyme- or CD 14-reactive cells) were identified among other mononuclear cell types in islet infiltrates. V beta 8-positive T cells were overrepresented, but T cells with other V beta s studied (V beta 5, V beta 5.1, V beta 6, V beta 12) were also found. The vascular endothelium of the islets and many small vessels nearby islets strongly expressed intercellular adhesion molecule-1, whereas vascular cell adhesion molecule-1 and E-selectin were totally absent. We conclude: (a) that increased expression of intercellular adhesion molecule-1 on vascular endothelium may increase endothelial adhesion of mononuclear cells and enhance their accumulation in the pancreas during diabetic insulitis; (b) that T cells with certain T cell receptors can be enriched in infiltrated pancreatic islets; and (c) that macrophages and antigen-specific CD 8-positive T cells are involved in pancreatic beta cell destruction at the onset of IDDM.

Antigens, CD↗
PubMed1991

Regulation of lymphocyte traffic to mucosa-associated lymphatic tissues.

Lymphocyte recognition and binding to endothelial cells at sites where lymphocytes exit the blood is controlled by several molecules. At mucosal sites, the lymphocytes use at least VLA-4, CD44, and LFA-1 (CD18/CD11a) to bind the endothelial cell ligand molecules. The endothelial cell surface ligand for CD44 is probably a human equivalent of MECA-367 and hyaluronate. LFA-1 can bind to ICAM-1/ICAM-2; and VLA-4, to VCAM-1 on endothelium. However, for physiologic lymphocyte migration, these molecules may still need additional ligands that are currently uncharacterized. At sites of inflammation, cytokines increase the expression of ICAM-1, VCAM-1, and a third endothelial cell antigen, ELAM-1, whose counter-receptor on leukocyte surface is presently unknown. Upregulation of these molecules apparently facilitates the traffic of lymphocytes and other leukocytes to sites of inflammation, thus partially determining the nature and extent of inflammation. These same molecules may be equally responsible for the pathologic characteristics of the immune response seen, for example, in inflammatory bowel diseases.

Animals↗
PubMed1985

[Hydatid cyst of the thyroid. Apropos of 2 cases].

Two cases of hydatid cyst of the thyroid are reported and the rare cases in the literature reviewed. Hydatidosis located in the thyroid is an infrequent finding, even in endemic countries. Finding on clinical examination are usually those of a cold thyroid nodule, and diagnosis is by detection of other sites for the lesion, positive results of immunologic tests, or often only after histology of an operative specimen. The spontaneous course of the affection may be interrupted by complications due either to the size of the lesion or the parasite itself. Treatment is surgical, usually by a hemithyroidectomy.

Adolescent↗
PubMed1982

Haema synthesis during pyridoxine therapy in two families with different types of hereditary sideroblastic anaemia.

The activity of delta-aminolaevulinic acid synthase (ALA-S) as well as the concentrations of coproporphyrin and protoporphyrin in peripheral red blood cells were examined in 2 sisters and in 2 brothers with hereditary sideroblastic anaemias (HSA) of different types. The measurements were done before and during treatment by pyridoxal-5-phosphate (PLP) and/or pyridoxine chloride. Previous family studies indicated an X chromosome linked HSA in the 2 brothers, whereas the precise mode of inheritance in the 2 sisters has not been established. Previous and present studies have revealed no characteristic defect in haema synthesis in the 2 sisters and their treatment by PLP or pyridoxine produced no haematologic response although a slight stimulation of haema synthesis was observed. In contrast, the 2 brothers showed decreased activity of ALA-S and decreased protoporphyrin concentration in peripheral red blood cells. After treatment by PLP and/or pyridoxine the ALA-S activity was restored to normal. Corresponding to the stimulation of haema synthesis a partial haematological response was observed in both brothers. Stopping and restarting of pyridoxine therapy in one brother confirmed the above results. These observations indicate the presence of two genetically and biochemically different types of HSA and help us to understand the varying response to pyridoxine therapy in this rare disorder.

5-Aminolevulinate Synthetase↗
PubMed1980

New method for liquid-chromatographic measurement of erythrocyte protoporphyrin and coproporphyrin.

We describe a "high-pressure" liquid-chromatographic method for separating all the porphyrins in the heme biosynthetic pathway. The preliminary extraction and purification method is such that only erythrocyte porphyrins with fewer than five carboxyl groups, which includes protoporphyrin and the much smaller amount of coproporphyrin present, are measured. The porphyrins extracted from erythrocytes are chromatographically separated by use of a simple eluent system and fluorometrically detected.

Adult↗
PubMed1979

Radioisotope X-ray fluorescence technique in the study of joint inflammation.

An X-ray fluorescence technique was employed to study the clearance rate from the knee joint of an intraarticularly injected stable tracer. Clearance curves, determined in two normal volunteers and in three patients with various articular diseases, were found to be of the monoexponential type in agreement with results obtained by authors employing radioactive tracers. Clearance half-time values in basal conditions were higher in the normal knee joint than in the inflamed knee joint. The effect of a corticosteroid suspension injected into the knee joint was also studied. Preliminary results obtained indicate that the X-ray fluorescence technique can be employed, with some advantages compared with the radiotracer technique, for quantitative determination of spontaneous or pharmacologically induced changes in joint inflammation.

Humans↗
PubMedDate not supplied

A mouse molecular mimic of human vascular adhesion protein-1.

Human vascular adhesion protein-1 (VAP-1) is an endothelial sialoglycoprotein which exists in forms of Mr 90000 and 170000 and mediates lymphocyte binding to vessels under shear. VAP-1 is functionally defined by an inhibitory mouse mAb 1B2. A large-scale immunoaffinity purification of VAP-1 from human tonsil lysates was performed to determine the protein sequence for VAP-1 cDNA cloning. A dominant protein of molecular weight 90000 was obtained which yielded an N-terminal sequence of 20 amino acids which bore no significant identity to any protein sequence in the data banks. A mouse mAb (5B11) against a synthetic peptide from this sequence was raised and found to stain tissues in an identical manner to mAb 1B2, to inhibit lymphocyte adhesion to endothelial cells and to recognize VAP-1. Later, the N-terminal sequence obtained from the 1B2 immunoprecipitations was found to be identical to a mouse cyclophilin C associated protein (mCyCAP) subsequently published by others. We show here by several criteria at the protein and DNA level that VAP-1 is distinct from mCyCAP. Moreover, we elucidate the mechanism which results in binding of mCyCAP to mAb 1B2 during antibody synthesis in hybridoma cells and the sequelae of co-precipitation of mCyCAP during the immunoaffinity chromatography. Binding of mCyCAP to a mouse mAb has not been described before and suggests a new function for this molecule in immunoglobulin synthesis and/or secretion. Moreover, these data indicate that the N-terminal peptide of mCyCAP is a molecular mimic of a functionally important epitope of VAP-1.

Amine Oxidase (Copper-Containing)↗