Disease relevance of Granuloma

• In studies of function, lung T cells from patients with sarcoidosis and high-intensity alveolitis released monocyte chemotactic factor (a lymphokine critical to granuloma formation) and polyclonally activated B cells to produce immunoglobulins [1].
• Chronic granulomatous disease (CGD) is a recessive disorder characterized by a defective phagocyte respiratory burst oxidase, life-threatening pyogenic infections and inflammatory granulomas [2].
• Here we report that the immunoregulatory cytokine tumour necrosis factor alpha is necessary and sufficient to reconstitute granuloma formation in schistosome-infected SCID mice [3].
• Chlorpropamide-induced granulomas. A probable hypersensitivity reaction in liver and bone marrow [4].
• Our results demonstrate induction of dosR (Rv3133c) and 20 other members of the DosR regulon believed to mediate the transition into dormancy, and that rel(Mtb) is required for Mycobacterium tuberculosis survival during extracellular persistence within host granulomas [5].

Psychiatry related information on Granuloma

• Alcohol consumption significantly reduced by 25% the mean granuloma diameter and by about 60% the extent of fibrous tissue deposition determined chemically as hydroxyproline [6].
• The other patient had a thorotrast granuloma and angiosarcoma of the liver after 22 year and 28 year latency periods respectively [7].

High impact information on Granuloma

• Moreover, culture supernatants from activated gamma delta T lymphocytes induce adhesion and aggregation of bone-marrow monocytes in the presence of granulocyte monocyte-colony stimulating factor (CSF), suggesting that products of gamma delta-bearing T cells may play a role in the immune response, possibly by stimulating granuloma formation [8].
• In humans, interferon gamma (IFN-gamma) receptor deficiency leads to a predisposition to mycobacterial infections and impairs the formation of mature granulomas [9].
• Thus, IL-12-dependent IFN-gamma secretion in humans seems essential in the control of mycobacterial infections, despite the formation of mature granulomas due to IL-12-independent IFN-gamma secretion [9].
• When two new steroids, methyl prednisolonate and methyl 20-dihydroprednisolonate, were applied locally their anti-inflammatory activities were nearly equivalent to those of the parent compound prednisolone in the cotton pellet granuloma bioassay [10].
• Using intestinal parasite infection and a pulmonary granuloma model, we demonstrate cryptic roles for IL-4, IL-5, IL-9, and IL-13 in these responses [11].

Chemical compound and disease context of Granuloma

• WSX-1(-/-) mice also showed poorly differentiated granulomas with dispersed accumulations of mononuclear cells when infected with bacillus Calmette-Guerin (BCG) [12].
• At 10 1/2 months, polytef granulomas were found at all injection sites and some sites of distant migration [13].
• To our knowledge, this is the first report of a patient with liver and bone marrow inflammation characterized by granulomas with eosinophilic infiltration following intake of chlorpropamide [4].
• Daily subcutaneous treatment of mice with 0.5 mg of hydrocortisone beginning simultaneously with pristane injection prevents the increase in the peritoneal cell population, granuloma formation, d the production of a conditoned environment [14].
• Supernates from the cultured granuloma cells contain factor(s) which induce the proliferation of thymocytes; the release of such factors by the cells is stimulated by lipopolysaccharide [15].

Biological context of Granuloma

• Interestingly, the dormancy phenotype of extracellular M. tuberculosis within host granulomas appears to be immune mediated and interferon-gamma dependent [5].
• This was accompanied by accelerated infiltration of memory T cells into the periphery of hepatic granuloma sites, most of them were in cell cycle and further produced higher amount of IFN-gamma leading to exacerbation of liver injury [16].
• The tumors develop in peritoneal granulomas and are characterized by Myc-activating T(12;15) chromosomal translocations and, most frequently, by secretion of IgA [17].
• Progesterone receptors appear in granuloma cells of preovulatory follicles after the midcycle gonadotropin surge, suggesting important local actions of progesterone during ovulation in primates [18].
• Infected TNFRp55-/- mice treated with a control mAb became moribund between days 26 and 34 postinfection, showing widespread inflammatory cell apoptosis within disintegrating granulomas [19].

Anatomical context of Granuloma

• The activities of 5'-nucleotidase and leucine aminopeptidase in the cultured granuloma cells showed that they resembled macrophages from thioglycollate-stimulated mice but not unstimulated macrophages in these respects [15].
• Using a primary pulmonary granuloma model, induced with Schistosoma mansoni eggs, we demonstrate that granuloma formation, characterized by eosinophil infiltration, is abrogated in T1/ST2-deficient mice [20].
• Depletion of IFN-gamma or natural killer cells resulted in a marked enhancement of granuloma formation around intravenously injected eggs and was associated with increased Th2 and decreased Th1 and interleukin (IL)12 mRNA expression [21].
• Treated mice demonstrated a decrease in granuloma size in the liver, colon, and ileum, and hydroxyproline concentration of isolated liver granulomas was increased [22].
• RESULTS: NOD2 was detected readily in monocytes, but not in mature macrophages in the lamina propria or within granulomas, and levels declined as monocytes differentiated into macrophages in vitro, so that Caco-2 cells expressed more NOD2 mRNA than macrophages [23].

Gene context of Granuloma

• In parallel, the livers of IFN-gamma R0/0 mice showed a reduction in the formation of characteristic granulomas at 2 wk after inoculation [24].
• Using a pulmonary granuloma model, induced with Schistosoma mansoni eggs, we demonstrate that although eosinophil infiltration, immunoglobulin E, and IL-5 production are reduced in the IL-4-deficient mice and IL-13-deficient mice, they are abolished only in the combined absence of both cytokines [25].
• IL-1 beta and IL-1ra were produced by submucosal granulomas and correlated with inflammation [26].
• Remarkably, CSD granulomas in vivo contain CXCL13-producing DCs [27].
• Inflammation, as measured by granuloma size, also increased significantly in the absence of P-selectin [28].
• Collectively, our data provide what we believe are novel insights into the involvement of F4/80+ DC-like cells in intestinal granuloma formation and demonstrate the role of host (IL-4 and IgG) and environmental (enteric flora) factors that regulate this function [29].
• We conclude that IFN-gamma causes a dysbalance between angiostatic and angiogenic mediators and a concomitant reduction in granuloma vascularization, but that CXCR3-targeted chemokines are not sufficient to induce granuloma necrosis in a mouse model of mycobacteria-induced immunopathology [30].

Analytical, diagnostic and therapeutic context of Granuloma

• Neutralization of TNF has been shown to decrease recruitment of inflammatory cells and granuloma formation in several animal models [31].
• Hepatic fibrin-ring granulomas were found in a 35-yr-old man who developed fever, myalgias, rash, eosinophilia, and abnormal liver function tests 4 wk after the beginning of allopurinol treatment [32].
• Paw granuloma induced in mice by heat-killed mycobacteria was inhibited by oral administration of probucol, an effect that may be attributable to inhibition of IL 1 secretion [33].
• Distinct PCR products were identified in epithelioid granuloma in all 9 PBC cases [34].
• Immunohistochemistry demonstrated that iNOS was selectively expressed by the epithelioid and multinucleated giant cells within the granulomas [35].

References