Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat kidneys were perfused with anti-intercellular adhesion molecule-1 (anti-ICAM-1) monoclonal antibody prior to allotransplantation. In the two strain combinations examined, LEF-to-WKAH transplants resulted in accelerated graft loss, and no prolongation of graft survival. The accelerated graft loss was the result of frequent occurrence of necrotizing arteritis within the grafts. In contrast, TO-to-WKAH transplants resulted in no change in graft survival and no arteritis. Necrotizing vasculitis in the LEJ-to-WKAH grafts was characterized by fibrinoid necrosis, collection of cellular infiltrates and serum macromolecular protein entrapment. The F(ab1)2 form of anti-ICAM-1 antibody partially preserved the antibody's capacity to accelerate graft loss. Therefore, although endothelial injury by Fc-mediated cytotoxicity may be involved in vascular damage, other mechanisms also come into play. The amount and distribution pattern of ICAM-1 antigen were identical in both TO and LEJ strains. Intravenous anti-ICAM-1 antibody administration combined with lipopolysaccharide, Poly(I)-Poly(C), warm ischemia to the kidney, or subcutaneous immunization with allogeneic spleen cells, but without renal transplantation, did not generate necrotizing vasculitis or proteinuria. These observations plus our previous data on the rat liver transplantation model clearly show that graft perfusion with anti-ICAM-1 monoclonal antibody invokes extensive vascular damage within allografts by Fc-mediated and Fc-independent mechanisms, depending on the donor-to-host combination.
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PMID:Strain combination-dependent genesis of necrotizing arteritis in anti-ICAM-1 antibody-perfused renal allografts in the rat. 778 89

Severe Plasmodium falciparum malaria is characterized by multiple organ involvement due to sequestration of infected erythrocytes in small vessels. Endothelial cell adhesion molecules play an important role in this interaction. During the course of a severe cerebral P. falciparum malaria infection we found very markedly elevated levels of the soluble adhesion molecules intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1, with a maximum increase of nine, seven, and eight times, respectively. These very high levels of soluble adhesion molecules point to an endothelial cell injury as an additional cause to physiological release or shedding due to receptor interactions. Soluble thrombomodulin (sTM) levels showed an extremely marked elevation up to 332 ng/ml (up to 13 times the normal value) as well. Malaria patients without severe organ involvement/cerebral manifestation showed only a mild elevation of sTM levels. TM is a parameter independent of the immunological system. It is regarded as a marker of vasculitis and endothelial cell destruction. Therefore, markedly elevated sTM levels document a substantial endothelial cell injury in severe malarial infection and may be of diagnostic and prognostic importance.
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PMID:Serum levels of adhesion molecules and thrombomodulin as indicators of vascular injury in severe Plasmodium falciparum malaria. 781 16

Two types of autoantibodies and intercellular adhesion molecule-1 (ICAM-1) were measured in patients with vasculitis. There were 13 patients with systemic vasculitis, and 12 with cutaneous vasculitis. The measured antibodies included antiendothelial cell antibodies (AECA) and anti-cardiolipin (ACL) antibodies of three isotypes. Results showed that patients with systemic vasculitis had elevated levels of ICAM-1 and IgG isotype ACL antibodies. Higher levels of ICAM-1 and IgG isotype ACL antibody were found in patients with systemic vasculitis than in those with cutaneous vasculitis. Levels of ICAM-1 and IgG isotype ACL antibodies also decreased after disease activity subsided in patients with systemic vasculitis. Measurement of ICAM-1 and autoantibodies may be useful in evaluating the extent of involvement, and for following the disease course.
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PMID:Measurement of anti-endothelial and anti-cardiolipin autoantibodies and intercellular adhesion molecules-1 in patients with systemic and cutaneous vasculitis. 799 80

Circulating intercellular adhesion molecule-1 (ICAM-1) and 3 types of autoantibodies were measured in 30 patients with angiographical or pathological proved vasculitis. There were 18 patients with systemic vasculitis and 12 patients with cutaneous vasculitis. The measured antibodies included anti-endothelial cell antibodies (AECA), anti-cardiolipin (ACL) antibodies of 3 isotypes and anti-neutrophil cytoplasma antibodies (ANCA). The results showed that patients with systemic vasculitis had elevated levels of ICAM-1, AECA and IgG isotype antibody as compared with none or lower in patients with cutaneous vasculitis. Levels of ICAM-1 and IgG isotype ACL antibodies also decreased significantly after disease activity subsided in patients with systemic vasculitis. Measurement of ICAM-1 and autoantibodies may be useful in evaluating the extent of involvement and in following the disease activity of patients with vasculitis.
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PMID:Circulating intercellular adhesion molecules-1 and autoantibodies including anti-endothelial cell, anti-cardiolipin, and anti-neutrophil cytoplasma antibodies in patients with vasculitis. 825 40

In renal biopsy specimens from 15 patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated renal vasculitis, the infiltrating intraglomerular and interstitial leukocytes were localized and the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and the cytokine interleukin-1 alpha (IL-1 alpha) were studied by an immunohistochemical method. Intraglomerular leukocytes were mainly macrophages (13.46 +/- 9.29 cells/glomerular cross-section) and, to a lesser extent, T lymphocytes (4.61 +/- 2.81 cells/glomerular cross-section). Staining with VCAM-1, which was negative in the undamaged tufts, was strongly positive in necrotizing-extracapillary lesions. Staining with ICAM-1 was also present in the damaged tufts, but its pattern was more diffuse. Intraglomerular IL-1 alpha was found in all biopsy specimens. Where the Bowman's capsule was not damaged, the periglomerular infiltrating cells were macrophages (42.6 +/- 25.2 cells/glomerular cross-section) and T lymphocytes (51.06 +/- 33.0 cells/glomerular cross-section). When there was a granulomatous lesion involving the glomerulus, the number of cells per granulomatous area revealed a massive number of CD45-positive leukocytes (345.83 +/- 237.47 cells/granulomatous lesion), many of them positive for activity markers (HLA-DR, IL-2R), adhesion molecules, and IL-1 alpha. Many activated cells were also present in interstitial areas of perivascular clusters of leukocytes, in which T lymphocytes (prevalently CD4+ cells) outnumbered the macrophages (331.55 +/- 207.85 cells/0.05 mm2 area v 125.68 +/- 60.57 cells/0.05 mm2 area). Adhesion molecules and IL-1 alpha were found in both tubular and vascular areas in all biopsy specimens. Our data strongly support the involvement of both the adhesion molecules ICAM-1 and VCAM-1 in the recruitment of intraglomerular leukocytes in renal vasculitis, indicate that VCAM-1 is a very good marker of necrotizing-extracapillary damage, and suggest its crucial connection with the macrophage recruitment in these vasculitic lesions. The presence of histochemically detectable levels of IL-1 alpha in glomeruli, tubules, and vessels and on some inflammatory cells supports its involvement in the vasculitic lesions, probably by triggering a positive feedback that increases the damage.
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PMID:Intraglomerular and interstitial leukocyte infiltration, adhesion molecules, and interleukin-1 alpha expression in 15 cases of antineutrophil cytoplasmic autoantibody-associated renal vasculitis. 854 38

Plasma concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin) and intercellular adhesion molecule-1 (sICAM-1) were measured by enzyme-linked immunosorbent assay in four groups of children. Group 1 consisted of 20 patients with acute diarrhoea-associated haemolytic uraemic syndrome (D+HUS), the aetiology of HUS being verocytotoxin-producing Escherichia coli infection in each case. Controls consisted of 11 patients who had previously had D+HUS (group 2), 12 with chronic renal failure (group 3) and 8 healthy controls (group 4). When compared with healthy controls, the acute D+HUS group had higher sVCAM-1 (median 1,875 ng/ml, range 1,200-6,450 ng/ml vs. 1,200 ng/ml, range 975-2,125 ng/ml), von Willebrand factor antigen, (1.9 U/ml, range 0.85-5.1 U/ml vs. 0.55 U/ml, range 0.3-1.57 U/ml), white cell count (WBC, 14.5 x 10(9)/l, range 7.8-43.1 10(9)/l vs. 8.9 10(9)/l, range 5.7-10.8 10(9)/l) and neutrophil count (PMN, 10.1 x 10(9)/l, range 4.3-26.5 10(9)/l vs. 4.3 10(9)/l, range 3.7-6.6 10(9)/l), all P < 0.005, and sICAM-1 was reduced (230 ng/ml, range 130-340 ng/ml vs. 400 ng/ml, range 260-690 ng/ml), P < 0.05. Within the acute D+HUS group there was a significant correlation between sICAM-1 and PMN (r = 0.56, P < 0.01). There was no correlation between any adhesion molecule and plasma creatinine or von Willebrand factor. Comparing the acute HUS group with children with chronic renal failure, WBC (P < 0.001), PMN (P < 0.01) and sVCAM-1 (P < 0.01) were significantly elevated, but there was no difference between the von Willebrand factor (P = 0.08) or the sICAM-1 (P > 0.1). sVCAM-1 is elevated and sICAM-1 decreased in acute D+HUS. This pattern of altered adhesion molecule concentration is unlike that in adults with vasculitis and suggests that different endothelial regulatory factors are at play.
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PMID:Soluble circulating cell adhesion molecules in haemolytic uraemic syndrome. 858 13

Glucan-induced pulmonary granulomatous vasculitis in the rat mimics several human lung diseases (e.g., Wegener's granulomatosis, intravenous talcosis). We sought to clarify the role of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of glucan-induced granulomatous vasculitis. Immunohistochemical analysis of lung sections from rats with florid vasculitis (48 hours) revealed marked alveolar septal and lesional expression of ICAM-1. An ex vivo binding analysis with isotope-labeled antibodies and lung sections taken at various times up to 48 hours after glucan infusion revealed a progressive increase in whole-lung ICAM-1 expression. In vivo measurements of vascular wall-associated ICAM-1 expression revealed an earlier rise that began less than 6 hours after glucan infusion, peaked at 24 to 48 hours, and then declined to near baseline during the ensuing 24 to 96 hours. To assess whether ICAM-1 expression both within blood vessel walls and within lesions per se is important in granuloma development, we carried out in vivo neutralization experiments with several different routes of administration of antibody to ICAM-1. Monoclonal antibody to rat ICAM-1 was either infused intravenously at time 0 (when glucan was infused), infused intravenously at time 0 and after 24 hours, instilled only intratracheally 24 hours after glucan infusion, or given both intravenously (time = 0 and 24 hours) and intratracheally (time = 24 hours). Infusions of monoclonal antibody to rat ICAM-1 resulted in dose-dependent reductions in mean granuloma number and cross-sectional area. Intrapulmonary instillation of antibody to rat ICAM-1 (via tracheostomy 24 hours after glucan infusion) resulted in a modest reduction in mean granuloma number and cross-sectional area. When antibody to ICAM-1 was both infused and instilled via the trachea, we found an additive reduction in mean granuloma size and number. There was a 12-fold increase in adhesion of ED-1-positive peripheral blood mononuclear cells (monocytes) to granuloma-bearing frozen lung sections prepared 48 hours after glucan infusion. Moreover, 73% of the additional adherent monocytes were bound specifically to granulomas per se. The increase in ex vivo monocyte binding to lung sections prepared at 48 hours was reduced 62% when sections were incubated with monoclonal antibody to ICAM-1. Taken together, these data indicate that ICAM-1 expression in evolving glucan-induced granulomatous vasculitis occurs first within blood vessel walls and then within lesional cells per se. The in vivo blocking studies suggest that ICAM-1 expression in both anatomic sites is important in granuloma development.
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PMID:Role of intercellular adhesion molecule-1 in glucan-induced pulmonary granulomatosis in the rat. 876 14

The expression of the intercellular adhesion molecule-1 (ICAM-1) and its ligand lymphocyte function associated antigen-1 (LFA-1 or alpha L), the vascular cell adhesion molecule-1 (VCAM-1), endothelial leukocyte adhesion molecule-1 (ELAM-1), and the cellular receptors for extracellular matrix, alpha 1, alpha 2, alpha 3, alpha 5, alpha 6, alpha V, beta 1, and beta 3 integrin subunits, was studied in 28 patients with crescentic glomerulonephritis (GN) related to several mechanisms: four patients with anti-glomerular basement membrane antibodies or anti-GBM disease; 16 with immune complex mediated GN; and eight with pauci-immune GN, associated with vasculitis in four cases. A three-step immunoperoxidase technique was used on sections obtained from frozen renal biopsies. At the initial stage of evolution of the lesions, all the cells of the crescents expressed the beta 1, beta 3, alpha 1, alpha 3, and alpha V subunits of integrins, ICAM-1, and VCAM-1, and some cells expressed the alpha 2, alpha 5, alpha 6, and alpha L subunits of integrins along the plasma membrane. At a later stage, when the crescents were fibrocellular, alpha 3 and alpha 1 subunit expression was polarized, localized mainly in front of the extracellular matrix. In fibrotic crescents, the alpha 2, alpha 5, alpha 6, and alpha L chains were no longer detected, and VCAM-1 and ICAM-1 expression was decreased. VCAM-1 and ELAM-1 appeared on endothelial cells of peritubular capillaries in relation to the appearance of infiltrating inflammatory cells. The results of this study show that several adhesion molecules were expressed on cells forming crescents and were modified during crescent evolution; that these molecules were up-regulated on endothelial cells in relation to the severity of the inflammatory response; and that whatever the mechanism of the glomerulonephritis, adhesion molecule expression was identical. It can be postulated that adhesion molecules play a role in crescentic glomerulonephritis. Better knowledge of these molecules in human glomerulonephritis may open the way to a new therapeutic approach.
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PMID:Adhesion molecules in human crescentic glomerulonephritis. 886 90

MRL/MpJ-Fas(lpr) (Fas(lpr)) mice develop a rapidly fatal form of systemic autoimmune disease characterized by glomerulonephritis and vasculitis similar to severe cases of systemic lupus erythematosus in humans. To evaluate the requirement for intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of tissue injury in this model, we created ICAM-1-deficient MRL/MpJ-Fas(lpr) (ICAM-1/Fas(lpr)) mice. ICAM-1 deficiency resulted in a striking improvement in the survival of Fas(lpr) mice (median +/- SEM survival of Fas(lpr) = 26 +/- 1.7 vs ICAM-1/Fas(lpr) = 47 +/- 2.4 wk, p < 0.0001) and the increased survival was associated with delayed elevations of blood urea nitrogen levels in the ICAM-1/Fas(lpr) mice. Histologic examination of the ICAM-1/Fas(lpr) mice revealed an overall reduction in glomerular disease and a significant reduction in vasculitis in the kidney, lung, skin, and salivary glands when compared with Fas(lpr). These findings indicate that ICAM-1 plays a major role in development of glomerular and vascular injury in Fas(lpr) mice.
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PMID:Intercellular adhesion molecule-1 deficiency protects MRL/MpJ-Fas(lpr) mice from early lethality. 925 74

Cocaine has wide-ranging effects on the immune and neuroendocrine systems (Fiala et al., 1996) resembling an inflammatory "stress" response with upregulation of pro-inflammatory cytokines and stimulation of the HPA axis (Gan et al., 1997). Cocaine abuse has also been associated with vascular pathology, including vasculitis, vasospasm and hemorrhage. These effects suggest that cocaine could perturb the function of endothelial cells, including the blood-brain barrier, and influence the progression to AIDS in HIV-infected individuals (Shapshak et al., 1997; Goodkin et al., 1997). In order to understand clinical consequences of cocaine abuse, it is important to gain insight into molecular and cellular basis of cocaine's effects on immune and endothelial cells. Cocaine's in vitro effects on (a) permeability, (b) immune cell migration, (c) adhesion molecules, and (d) cytokine expression were investigated in a blood-brain barrier model constructed with brain microvascular endothelial cells and fetal astrocytes with the following results: (a) cocaine and tumor necrosis factor-alpha (TNF-alpha) increased the model's permeability to inulin similarly in a dose-responsive fashion; (b) cocaine (10(-4) to 10(-8_ M) enhanced monocyte migration across the barrier with the maximum increase, approximately 100%, by 10(-5) M cocaine; (c) cocaine treatment also increased the expression of endothelial adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecules-1 (VCAM-1) and platelet/endothelial cell adhesion molecule-1 (PECAM-1); (d) although the cocaine in vitro effects on cytokine production by mononuclear cells have been difficult to assess due to a heterogeneity in the degree of responsiveness between individuals, the data suggest that mononuclear cells from cocaine addicts are sensitized to in vitro cocaine challenge with hypersecretion of inflammatory cytokines. Cocaine's in vivo manifestations are compatible with these in vitro effects: (A) chronic cocaine treatment of rats significantly increased rolling white blood cell flux, leukocyte-endothelium adhesion, and ICAM-1 expression in the mesentery (House et al., 1996); (B) cocaine injection to cocaine-dependent subjects tipped the balance of cytokine secretion by mononuclear cells to Th1-type (Gan et al., 1997), and (C) cocaine injection stimulated the hypothalamic-pituitary axis (HPA) to increase both anti- and pro-inflammatory hormonal secretion. Collectively, these results suggest that the immune effects of cocaine on endothelial, immune and neuroendocrine cells impair the function of the blood-brain, barrier, increase cell emigration from the blood vessels, in particular into the brain, and may cause vasculitis. These effects could also increase importation of HIV-1 into the brain.
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PMID:Cocaine enhances monocyte migration across the blood-brain barrier. Cocaine's connection to AIDS dementia and vasculitis? 966 72


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