Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extrinsic allergic alveolitis (EAA) (synonym: hypersensitivity pneumonitis) is a hypersensitivity lung disease characterized by lymphocytic infiltrates in the pulmonary interstitial tissues. We have previously reported that the numbers of lymphocytes in bronchoalveolar lavage (BAL) samples in this disease correlate with levels of cholesterol and neutral lipid-laden 'foamy' macrophages. We have also reported that the macrophages express an increased density of MHC class II antigens (in particular HLA-DQ) which are known to be essential for antigen recognition by T lymphocytes. The aim of the present study was to explore whether cholesterol is capable of enhancing the antigen-presenting function of mononuclear phagocytes by modulating the expression of HLA-D region products. Incubation of purified monocytes from healthy volunteers with cholesterol in serum-free medium induced a significant increase in both the percentages of monocytes expressing HLA-DQ (P less than 0.02) and in the intensity of expression of the three HLA-D sub-region products, HLA-DQ, -DP and -DR (P less than 0.02, less than 0.01, less than 0.05, respectively). The cholesterol pre-incubated monocytes also exhibited enhanced antigen-presenting function (P less than 0.05), compared with controls pre-incubated without cholesterol. These findings indicate that increases in cholesterol in the extracellular milieu may augment antigen presentation by modulating the expression of HLA-D region products on antigen-presenting cells. Apart from EAA, this observation may also have relevance to inflammatory mechanisms in atherosclerosis, where 'foamy' macrophages also occur in association with hypercholesterolaemia.
 ...
PMID:Enhancement of the antigen-presenting function of monocytes by cholesterol: possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis and atherosclerosis. 137 Sep 28

The early stages of atherosclerosis are characterized by penetration into the arterial intima by both T lymphocytes and monocytes. Some of these T lymphocytes show signs of activation, though the mechanisms by which they become activated are not known. The monocytes develop into macrophages and subsequently into foam cells filled with oxidized LDL (oxLDL)-derived lipids. OxLDL has been found to exert several proinflammatory effects, including enhanced adhesiveness of endothelial cells and monocytes, chemotaxis of monocytes and T cells, and T-cell activation. The enzyme-linked immunospot (ELISPOT) assay has been shown to be a sensitive method for detection of single cells secreting antibodies or cytokines. Here we have used this method to characterize the T-cell cytokine secretion pattern after exposure to oxLDL in vitro. In peripheral blood mononuclear cells from healthy donors (n = 27), a significantly enhanced number of INF-gamma-producing cells was detected by ELISPOT (P < .001) after stimulation with 5 micrograms/mL oxLDL. In contrast, production of interleukin-4 was not significantly enhanced after stimulation with oxLDL. OxLDL-induced IFN-gamma secretion and T-cell proliferation were completely inhibited by major histocompatibility complex (MHC) class II antibodies. Furthermore, oxLDL was found to enhance the antibody secretion, indicating B-cell activation. Our results indicate that oxLDL activates T cells by an MHC class II-dependent mechanism. In healthy individuals, oxLDL induces IFN-gamma, which is produced by T helper type 1-like cells. These findings demonstrate that oxLDL induces a cell-dependent immune reaction, which may play an important role in the development of atherosclerosis.
 ...
PMID:Oxidized LDL induces enhanced antibody formation and MHC class II-dependent IFN-gamma production in lymphocytes from healthy individuals. 758 30

Immunocytochemical analysis of human saccular aneurysms, commonly referred to as berry aneurysms, was performed on formalin-fixed, paraffin-embedded sections using monoclonal antibodies with single and double staining methods. Atherosclerotic lesions were detected in all aneurysms, which ranged in size from 2 mm to 3 cm in diameter. Changes consistent with the earliest stages of atherogenesis, so-called "fatty streaks," were not detected. In the smallest aneurysms, atherosclerotic lesions were characterized by diffuse intimal thickening composed predominantly of proliferating smooth muscle cells (SMC) with a small number of macrophages and lymphocytes. Large aneurysms had advanced atherosclerotic lesions with cellular infiltrates composed mostly of macrophages, more mature looking SMC and a greater number of lymphocytes. Major histocompatibility complex (MHC) class II expression was detected predominantly in macrophages in all aneurysms. Some SMC in advanced atherosclerotic lesions, but not in diffuse intimal thickening, had MHC class II immunoreactivity. A significant number of lymphocytes and NK cells were found at the site of aneurysmal rupture. The progression of atherosclerosis within the aneurysmal sac correlated positively with aneurysmal growth, and we speculate may have contributed to aneurysmal rupture. Some evidence also suggested a possible role of atherosclerosis in the formation of berry aneurysms.
 ...
PMID:Immunocytochemical studies of atherosclerotic lesions of cerebral berry aneurysms. 802 14

The intercellular adhesion molecule (ICAM) 1 is an Ig-like cell adhesion molecule expressed by several cell types, including leukocytes and endothelial cells. It can be induced in a cell-specific manner by several cytokines, for example, tumor necrosis factor-alpha, interleukin-1, and interferon-gamma, and inhibited by glucocorticoids. Its ligands are the membrane-bound integrin receptors LFA-1 and Mac-1 on leukocytes, CD43, the soluble molecule fibrinogen, the matrix factor hyaluronan, rhinoviruses, and Plasmodium falciparum malaria-infected erythrocytes. ICAM-1 expression is predominantly transcriptionally regulated. The ICAM-1 promoter contains several enhancer elements, among them a novel kappa B element which mediates effects of 12-O-tetradecanoylphorbol-13-acetate, interleukin-1, lipopolysaccharide, tumor necrosis factor-alpha, and glucocorticoids. Expression regulation is cell specific and depends on the availability of cytokine/hormone receptors, signal transduction pathways, transcription factors, and posttranscriptional modification. ICAM-1 plays a role in inflammatory processes and in the T-cell mediated host defense system. It functions as a costimulatory molecule on antigen-presenting cells to activate MHC class II restricted T-cells, and on other cell types in association with MHC class I to activate cytotoxic T-cells. ICAM-1 on endothelium plays an important role in migration of (activated) leukocytes to sites of inflammation. ICAM-1 is shed by the cell and detected in plasma as sICAM-1. Regulation and significance of sICAM-1 are as yet unclear, but sICAM-1 is increased in many pathological conditions. ICAM-1 may play a pathogenetic role in rhinovirus infections. Derangement of ICAM-1 expression probably contributes to the clinical manifestations of a variety of diseases, predominantly by interfering with normal immune function. Among these are malignancies (e.g., melanoma and lymphomas), many inflammatory disorders (e.g., asthma and autoimmune disorders), atherosclerosis, ischemia, certain neurological disorders, and allogeneic organ transplantation. Interference with ICAM-1 leukocyte interaction using mAbs, soluble ICAM-1, antisense ICAM-1 RNA, and in the case of melanoma mAb-coupled immunotoxin, may offer therapeutic possibilities in the future. Integration of knowledge concerning membrane-bound and soluble ICAM-1 into a single functional system is likely to contribute to elucidating the immunoregulatory function of ICAM-1 and its pathophysiological significance in various disease entities.
 ...
PMID:Intercellular adhesion molecule-1. 883 67

Platelet-activating factor (PAF) is a phospholipid inflammatory mediator which is synthesized by a variety of cells, including monocytes, endothelial cells, mast cells and neutrophils. PAF acts via a recently cloned PAF receptor, present on monocytes and endothelial cells, but not on non-activated lymphocytes. IL-4 is mainly produced by T lymphocytes, and belongs to the Th2 subset of T helper cells. IL-6 is mainly a monocyte/macrophage-derived cytokine with multiple proinflammatory effects. We here report that PAF induces IL-4 production, as determined by ELISPOT. Antibodies to MHC class II inhibited the IL-4 stimulatory effects of PAF. PAF also had the capacity to induce IgA production, as determined by ELISPOT, and IL-6 production in peripheral blood mononuclear cells (PBMC) as determined by ELISA. These PAF-mediated effects were completely inhibited by a specific PAF-receptor antagonist, WEB 2170. Taken together, our data indicate that PAF activates T lymphocytes to IL-4 production by an indirect, monocyte-dependent mechanism dependent on MHC class II. PAF also enhances antibody formation and IL-6 production from PBMC. These findings indicate that PAF activates immune-competent cells, which may be of importance in inflammatory diseases such as asthma, vasculitis and atherosclerosis.
 ...
PMID:Induction of IL-4 by platelet-activating factor. 887 Jul 12

Cysteine proteases have traditionally been viewed as lysosomal mediators of terminal protein degradation. However, recent findings refute this limited view and suggest a more expanded role for cysteine proteases in human biology. Several newly discovered members of this enzyme class are regulated proteases with limited tissue expression, which implies specific roles in cellular physiology. These roles appear to include apoptosis, MHC class II immune responses, prohormone processing, and extracellular matrix remodeling important to bone development. The ability of macrophages and other cells to mobilize elastolytic cysteine proteases to their surfaces under specialized conditions may also lead to accelerated collagen and elastin degradation at sites of inflammation in diseases such as atherosclerosis and emphysema. The development of inhibitors of specific cysteine proteases promises to provide new drugs for modifying immunity, osteoporosis, and chronic inflammation.
 ...
PMID:Emerging roles for cysteine proteases in human biology. 907 57

Recent studies have revealed that atherosclerosis bears several similarities to chronic inflammation. One of the earliest events in both human and experimental atherosclerosis is adhesion of monocytes and T lymphocytes to endothelial surface followed by their migration into the intima. This intimal recruitment of blood derived cells, coupled with the enhanced endothelial permeability to plasma proteins, indicates a potential role for inflammatory mechanisms in early atherogenesis. Colocalization of T lymphocytes and macrophages in all stages of human atherosclerosis, from grossly normal prelesional intima to fully advanced atheromatous plaques, and expression of cytokines and MHC class II antigens by many types of cells of the lesion provide further evidence that atherosclerosis has both the inflammatory and immune nature. The presence of T lymphocytes and macrophages in pairs with a close contact to each other suggests that cognate cell to cell interaction also plays a pivotal role in the pathogenesis of atherosclerosis. It seems conceivable that the T lymphocyte-macrophage interaction particularly takes place in the areas where atherosclerotic lesions are in progress or being active. The pathogenic potentials of immunologic factors are fruitful subjects for further investigation.
 ...
PMID:Inflammatory and immunological nature of atherosclerosis. 911 27

Activated T lymphocytes are present in human atherosclerotic lesions and autoantibodies to antigens within lesions have been detected in serum, but the roles of the cellular and humoral immune systems in atherogenesis have not been determined. The effect of total lymphocyte deficiency on atherogenesis was investigated by crossing apo E-deficient mice (which develop atherosclerosis resembling human disease) with mice deficient in RAG2 (which is required for normal B and T lymphocyte development). Mice were placed on a fat- and cholesterol-enriched diet for 12 wk. RAG2-deficient mice had no serum autoantibodies, in contrast to the high titers in RAG2+/- littermates. There were no T lymphocytes and a markedly reduced number of MHC class II-positive macrophages in atherosclerotic lesions of RAG2-deficient mice. Despite these differences, RAG2-deficient mice developed atherosclerosis similar in extent to that in immunocompetent littermates, based on quantification by two independent methods. In conclusion, the absence of autoantibodies and T lymphocytes did not influence the extent of aortic atherosclerotic lesions in apo E-deficient mice.
 ...
PMID:The effects of total lymphocyte deficiency on the extent of atherosclerosis in apolipoprotein E-/- mice. 929 26

Several lines of evidence indicate that viral infections, particularly with cytomegalovirus (CMV), play a role in the pathogenesis of solid organ allograft rejection. A diagnostic feature of acute rejection is infiltration of allograft parenchyma by lymphocytes, a process regulated by induction of adhesion molecules on vascular endothelial cells and their ligand on leucocytes. Data derived from biopsies of CMV-infected transplant recipients, as well as from experimental models of transplantation, indicate that CMV infection can result in an upregulation of such adhesion molecules, thereby facilitating the inflammatory process. Infection with CMV is also associated with an increased expression of MHC class II on multiple cell types. Since recognition of nonself MHC antigens is the major determinant of allograft rejection, an upregulation of these molecules could contribute to graft failure. Infection with CMV has also been implicated in the induction of smooth muscle proliferation and intimal thickening, both hallmarks of transplant atherosclerosis, which constitutes the most common cause of heart allograft failure. CMV can be classified into four, possibly five, different genotypes based on restriction length polymorphism of the envelope glycoprotein B gene; these genotypes may exhibit varied geographic and demographic frequency distributions and also differ in their pathogenicity and cell tropism. Further studies are needed to evaluate these issues and in particular the genetic contribution of the recipient to CMV modulation of rejection.
 ...
PMID:Role of cytomegalovirus infection in allograft rejection: a review of possible mechanisms. 1054 37

A role for interferon-gamma (IFN-gamma) has been implied in the atherogenic process. To determine whether exogenously administered IFN-gamma exerts an effect on the development of atherosclerosis, we intraperitoneally administered either recombinant IFN-gamma (100 U/g body weight) or phosphate buffered saline daily for 30 days to atherosclerosis-susceptible apolipoprotein E-/- mice (16-week-old male mice, n = 11 per group) fed a normal diet. Atherosclerotic lesion size was quantified in the ascending aorta. The number of T lymphocytes and major histocompatibility complex (MHC) class II-positive cells within lesions were also quantified in this region. IFN-gamma administration reduced serum cholesterol concentrations by 15% (P = 0.02). For both groups, the majority of cholesterol was present in very low density lipoproteins, which were modestly reduced in mice receiving IFN-gamma. Despite the decrease in serum cholesterol concentrations, IFN-gamma injections significantly increased lesion size twofold compared to controls (119,980 +/- 18, 536 vs. 59,396 +/- 20,017 micrometer(2); P = 0.038). IFN-gamma also significantly increased the mean number of T lymphocytes (19 +/- 4 vs. 7 +/- 1 cells; P = 0.03) and MHC class II-positive cells (10 +/- 3 vs. 3 +/- 1 cells; P = 0.04) within lesions. These data lend further support to a pro-atherogenic role of IFN-gamma.
 ...
PMID:Exogenous interferon-gamma enhances atherosclerosis in apolipoprotein E-/- mice. 1110 54


1 2 3 4 Next >>