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R S Cotran

Publications and source records attributed to R S Cotran.

At least 55 records · Page 3Linked to original sources
PubMed1985

Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines.

Increased leukocyte adhesion to the endothelial lining of blood vessels is an essential event in inflammation and the pathogenesis of certain vascular diseases. We have studied the effect of interleukin 1 (IL-1), an inflammatory/immune mediator, on endothelial-leukocyte adhesion using quantitative in vitro assays. Selective pretreatment of cultured human umbilical vein endothelial monolayers with IL-1 (5 U/ml, 4 h) resulted in an 18.3 +/- 2.6-fold increase in human peripheral blood polymorphonuclear leukocyte (PMN) adhesion (mean +/- SEM, n = 16) and a 2.6 +/- 0.3-fold increase in monocyte adhesion (n = 7) over basal levels. IL-1-treated endothelial monolayers also supported increased adhesion of the promyelocytic cell line HL-60 and the monocytelike cell line U937 (33.0 +/- 6.0-fold, n = 6 and 4.9 +/- 0.5-fold, n = 15, respectively). In contrast, selective IL-1 pretreatment of leukocytes, or the addition of IL-1 during the adhesion assay, did not alter endothelial-leukocyte adhesion. Conditioned medium from IL-1-treated endothelial cultures also did not promote leukocyte adhesion to untreated monolayers. IL-1 induction of endothelial adhesivity was concentration dependent (maximum, 10 U/ml), time dependent (peak, 4-6 h), and reversible, was blocked by cycloheximide (10 micrograms/ml) or actinomycin D (5 micrograms/ml) but not by acetylsalicylic acid (100 microM), and occurred without detectable endothelial cell damage. IL-1 treatment of SV40-transformed human endothelial cells and dermal fibroblasts did not increase their adhesivity for leukocytes. These data suggest that IL-1 can act selectively on human vascular endothelium to increase its adhesivity for circulating blood leukocytes, and thus to localize leukocyte-vessel wall interactions at sites of inflammation in vivo.

Cell Adhesion↗
PubMed1985

Interleukin-1 activation of vascular endothelium. Effects on procoagulant activity and leukocyte adhesion.

Interleukin-1 (IL-1), an inflammatory/immune mediator, acts directly and selectively on cultured human vascular endothelial cells to alter two important functional properties. First, IL-1 induces endothelial cell biosynthesis and surface expression of a tissue factor-like procoagulant activity. Second, IL-1 dramatically increases the adhesiveness of the endothelial cell surface for human peripheral blood polymorphonuclear leukocytes (6-42-fold increase) and monocytes (2-5-fold increase), as well as the related leukocyte cell lines HL-60 and U937. These IL-1 effects are concentration-dependent (maximum, 5-10 U/ml), time-dependent (peak 4-6 hours), and reversible. Cycloheximide and actinomycin D block these IL-1 actions on endothelium, which suggests the requirement for de novo protein synthesis. Human-monocyte-derived IL-1, cell-line--derived IL-1, and recombinant IL-1 exhibited comparable biologic activities in our assays, whereas two other mediators, IL-2 and immune interferon, were without effect. IL-1 stimulated procoagulant activity and leukocyte adhesion in human endothelial cells cultured from both umbilical veins and adult saphenous veins but not in other cultured cell types, including SV-40-transformed human endothelial cells and human dermal fibroblasts. Similar actions of IL-1 on vascular endothelium in vivo may contribute to the development of intravascular coagulation and enhanced leukocyte--vessel wall adhesion at sites of inflammation.

Adhesiveness↗
PubMed1984

Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells.

Human monocyte-derived interleukin 1 (IL-1) was found to be a potent inducer of procoagulant activity in cultured human vascular endothelium. IL-1-induced human umbilical vein endothelial cell procoagulant activity (HEC-PCA) was transiently expressed, manifest in intact cell monolayers, and required protein synthesis. Data obtained with coagulation factor-deficient plasma and a goat anti-human apoprotein III antiserum suggested that most, if not all, of IL-1-induced endothelial cell procoagulant activity is tissue factor-like. IL-1 induction of HEC-PCA may be important in the pathogenesis of intravascular coagulation in a variety of immunological and inflammatory conditions.

Blood Coagulation↗
PubMed1984

Interactions of T lymphocytes with human vascular endothelial cells: role of endothelial cells surface antigens.

We have studied the interactions of peripheral blood T lymphocytes with cultured human vascular endothelial cells, focusing upon endothelial cell surface antigens important for T cell recognition. Under standard culture conditions endothelial cells express class I but not class II major histocompatibility complex (MHC) antigens. However, class II antigens may be induced by activated T cells or T cell products, including the lymphokine immune interferon. Immune interferon concomitantly increases class I antigen expression and causes a change in cell shape. In addition to vascular endothelial cells, we have found that vascular smooth muscle cells and human dermal fibroblasts may also be induced by immune interferon to express class II antigens. All known human class II antigens are induced (i.e. HLA-DR, DC and SB) as is the associated invariant chain. Induced antigen expression in these cells is stable over several days, although mRNA levels decline rapidly upon withdrawal of interferon. Vascular and stromal cell class II antigens are functional, in that they can be recognized by cytolytic and helper T cell clones. Several non-MHC antigens are also involved in the recognition of endothelial and stromal cells by T cells. We propose a model for the role of inducible class II molecules on endothelium and stromal cells in vivo: The induction of class II MHC antigens on endothelial cells, locally mediated by activated T cells, enables endothelium to present an immunogenic cell surface structure, comprised of antigen plus self class II polymorphic determinants, which in turn, serves to recruit additional antigen-specific T cells from the circulation into the site of a developing cell mediated immune response. Class II molecules on stromal cells, also induced locally at the site of a developing response, confers immune accessory function on these cells and may serve to augment and sustain a T cell response.

Antigen-Presenting Cells↗
PubMed1984

Focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis is an important cause of the nephrotic syndrome in children and adults. This paper reviews the pathogenesis, clinical manifestations, morphology, and treatment of focal glomerulosclerosis. In addition, it considers the recently described association of focal glomerulosclerosis with nonglomerular renal diseases and the possible role of this glomerular lesion in progressive renal failure.

Glomerulonephritis↗
PubMed1984

Modulation of Ia and leukocyte common antigen expression in rat glomeruli during the course of glomerulonephritis and aminonucleoside nephrosis.

We have investigated changes in the glomerular expression of two antigens, Ia and leukocyte common (LC) antigens, during the course of two models of glomerular injury in the rat. Acute glomerulonephritis induced by nephrotoxic, antiglomerular basement membrane antiserum is accompanied by a 3-fold increase in the number of glomerular cells expressing Ia and LC antigens. Acquisition of the Ia+ phenotype appears to occur in LC+ monocytes that have assumed subendothelial and intramesangial positions. Enhanced Ia expression is seen over a wide range of proteinuria. Decomplementation prior to nephrotoxic, antiglomerular basement membrane anti-serum administration abrogates both the proteinuria and the increased Ia expression; an increase in cells expressing LC antigen still occurs. The chronic phase of nephrotoxic, antiglomerular basement membrane antiserum-induced glomerulonephritis is associated with a persistent increase in glomerular Ia+ cells residing primarily in the mesangium. In the glomerulopathy induced by the aminonucleoside of puromycin, there are two phases of glomerular Ia modulation. In the first week, there is a decrease in Ia expression by LC+ cells. The second week is marked by infiltration by monocytes and an increase in Ia expression by both resident and infiltrating cells. Modulation of the Ia phenotype on resident and infiltrating marrow-derived cells carries implications with respect to the immunologic pathogenesis of both models of glomerular injury.

Animals↗
PubMed1983

Ia expression by vascular endothelium is inducible by activated T cells and by human gamma interferon.

We have used monoclonal antibody binding, measured by radioimmunoassay, fluorescence flow cytometry, and ultrastructural immunocytochemistry, to measure expression of Ia antigens on cultured human umbilical vein endothelial (HUVE) cells. Under standard culture conditions, HUVE cells do not express Ia antigens. However, treatment of primary HUVE cultures with phytohemagglutinin induces the expression of Ia antigens. Every endothelial cell in the culture becomes Ia-positive and endothelial cells appear to synthesize Ia. HLA-A,B is concomitantly increased. The expression of Ia appears to be mediated by T cells because (a) pretreatment of primary HUVE cultures with OKT3 plus complement blocks the action of the lectins but not of medium conditioned by lectin-activated peripheral blood mononuclear cells; (b) co-culture of endothelial cells with allogeneic T cells, in the absence of lectin, also induces endothelial Ia; and (c) human immune (gamma) interferon, produced by Chinese hamster ovary cells transfected with the human gamma interferon gene, directly induces endothelial Ia. During co-culture with lymphocytes, about one-third of the endothelial cells are Ia-positive after 24 h and all of the endothelial cells are Ia-positive by 72 h. Proliferation of allogeneic T cells starts by 96 h and peaks at 144 h. Thus, endothelial Ia appears sufficiently early to be a determinant for the proliferation of allogeneic T cells. Inducible expression of Ia by endothelium may be important both for allograft rejection and for recruitment of circulating T cells into the site of an immune response.

Cells, Cultured↗
PubMed1983

Monoclonal antibodies against rat glomerular antigens: production and specificity.

To define the characteristics and target antigens (Ags) of nephrotoxic antibodies (Abs) and to analyze the factors that govern the evolution of Ab-mediated glomerular injury, we have prepared monoclonal Abs against rat glomerular Ags. BALB/c mice were immunized with Lewis rat cortex or glomeruli, and their spleens were removed and fused with hypoxanthine-aminopterin-thymidine supplement-sensitive myelomas. Hybrids were selected for production of Abs against Lewis rat kidney by indirect immunofluorescence. To date, more than 50 positive hybrids have been selected and their tissue reactivity defined by indirect immunofluorescence and immunoelectron microscopy. Of these, 14 are presented here in detail. One of these monoclonal Abs, K9/4, recognizes a unique Ag present exclusively on the cell surface of rat glomerular visceral epithelial cells. Four Abs (K12/2, K17/4, K12/5, and K12/8) recognize sites within the glomerular basement membrane; K12/2 and K17/4 also bind to vascular basement membranes of the rat, whereas K12/5 and K12/8 bind to glomerular basement membrane, tubular basement membranes, and vascular and epithelial basement membranes in all tissues of the rat. Two hybridomas (K6/1 and K6/3) recognize determinant(s) present on cell surfaces of endothelial and epithelial cells as well as within the glomerular basement membrane. All of these previously mentioned Abs are species restricted (i.e., they bind only to rat tissue) and, with the exception of K9/4, bind upon in vivo administration. Several others, however, recognize ubiquitous Ags that are present on intracellular structures in every species tested. The tissue distribution of these Ags suggests that they are present in contractile or cytoskeletal elements and, as expected from their intracellular location, monoclonal Abs directed against these components do not bind upon in vivo administration. Future studies will be directed at defining the antigenic composition of the glomerular capillary wall and the relevance of such Ags in immune-mediated glomerular injury.

Animals↗
PubMed1983

Stimulation of human monocyte/macrophage-derived growth factor (MDGF) production by plasma fibronectin.

Culture supernatants from human peripheral blood monocytes, isolated free of platelet contamination and cultured in the absence of serum, stimulate DNA synthesis and cell growth in Balb/c 3T3 fibroblasts and bovine aortic smooth-muscle cells. Monocytes cultured in serum-free medium for 24 hours with plasma fibronectin, added as either a surface-attached or soluble molecule, secrete significantly increased amounts of growth-promoting activity. Fibronectin also stimulates an increase in intracellular growth factor content and in protein synthesis by monocytes. Both the enhanced growth-promoting activity and protein synthesis are inhibited by cycloheximide. Thus, fibronectin-monocyte interactions may influence the production of growth-promoting activity by monocytes and contribute to fibroblast and smooth-muscle replication in wound healing, chronic inflammation and atherosclerosis.

Cell Adhesion↗
PubMed1982

Tubulointerstitial nephropathies.

Significant tubulointerstitial disease is multifactorial in origin, and two or more causes may coexist in the same patient. Since removal of the responsible agent or agents is often curative, careful etiologic diagnosis is essential to effective management. Etiology and pathophysiologic mechanisms, therapeutic regimens, and prognosis for several of the various forms of the disease are discussed.

Analgesics↗
PubMed1982

Localization of an Ia-bearing glomerular cell in the mesangium.

Using trypsin to render intact, isolated rat glomeruli permeable to antibody, and using an electron microscopic immunoperoxidase technique, we have localized a phagocytic immunologically-relevant cell bearing Ia determinants to the renal mesangium. Thus there are at least two functionally distinct cell types in the renal mesangium: one is a contractile smooth musclelike cell, and the other a phagocytic cell that bears immunologically-relevant surface determinants.

Animals↗
PubMed1981

Characterization of resident glomerular cells in the rat expressing Ia determinants and manifesting genetically restricted interactions with lymphocytes.

The existence of a subpopulation of rat glomerular cells bearing Ia determinants has been demonstrated with the aid of techniques for the enzymatic isolation and culture of glomerular cells. The Ia-positive cell is normally resident in the uninflamed glomerulus. It resembles a mononuclear phagocyte and consists of a functionally heterogeneous cell population with the capacity of Fc receptor display and phagocytosis, both in vivo and in vitro. A new technique for labeling these cells in situ in intact glomeruli has indicated that Ia-positive cells make up approximately 2% of the total glomerular cell population. The isolated glomerular cells can take up antigen and stimulate immune lymphocytes in an I-region-restricted interaction. They are strongly stimulatory in an allogeneic primary mixed lymphocyte culture. Characterization of this cell type suggests potential new insights into the pathogenesis of renal allograft rejection and immunologically mediated glomerulonephritis.

Animals↗