Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019621 (Langerhans cell histiocytosis)
 3,250 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macrophages play important roles in immunity and inflammation, and in allergic, granulomatous and neoplastic diseases. Here, we present the indepth results of an ongoing study of macrophage differentiation pathways in cutaneous macrophage disorders and in vitro. Up to now, a total of 40 cases of cutaneous macrophage disorders (histiocytoses and granulomas) and related diseases were examined using a panel of monoclonal and polyclonal antibodies to macrophage differentiation antigens (mAb MS-1, mAb alpha CD1a, mAb alpha CD34, mAb RM 3/1, mAb alpha CD11c, mAb alpha CD36, mAb MAC 387, mAb 27E10, polyclonal antibodies alpha MRP-8 and -14, mAb alpha CD68, mAb 25F9, mAb DRC1-R4/23, and mAb 1F10). Of these, MS-1 high molecular weight protein, synthesized by non-continuous sinusoidal endothelial cells and highly dendritic perivascular macrophages in normal human organs, is the most specific macrophage differentiation marker. MS-1 high molecular weight protein is selectively expressed by cutaneous non-Langerhans cell histocytoses, and proves to be a valuable diagnostic tool for these diseases. MS-1 high molecular weight protein is not found in Langerhans cell histiocytosis cells, epithelioid cells in sarcoidosis, and palisading histiocytes in granuloma annulare. MS-1+ macrophages may be found intermingled in cellular type dermatofibroma and in foreign body granulomas; they differ from MS-1+ non-Langerhans cell histiocytosis cells by their highly dendritic morphology, and thus rather resemble the MS-1+ macrophages in normal skin. RM 3/1 antigen shows a similar, but broader expression pattern including non-Langerhans cell histiocytoses, xanthelasmata palpebrarum, foreign body granulomas, granuloma annulare, and cellular type dermatofibroma. Moreover, xanthelasmata palpebrarum paradigmatically represent a class of macrophage lesions with strong RM 3/1, but little MS-1 antigen expression. In sarcoidosis, RM 3/1+ macrophages are only found at the very periphery of epithelioid cell granulomas. In contrast, 25F9 antigen is strongly and consistently expressed in epithelioid cells of sarcoidosis, and in foreign body granulomas. In cultured human monocytes/macrophages, RM 3/1 antigen is expressed early on, while MS-1 high molecular weight protein and 25F9 antigen are late and very late macrophage differentiation antigens, respectively. Expression of RM 3/1 antigen and MS-1 high molecular weight protein is inducible by glucocorticoid and interleukin-4, and less so by interleukin-13 and interleukin-10, and combinations thereof, while 25F9 antigen seems to be less influenced by these agents. Interferon-gamma (and less so tumor necrosis factor-alpha) inhibit expression of all three antigens in cultured human monocytes/macrophages.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dissection of macrophage differentiation pathways in cutaneous macrophage disorders and in vitro. 774 70

Histological features of tuberculosis are caseation necrosis and epithelioid cell granuloma formation. Both phenomena are interpreted as expression of cellular immunity. Caseation necrosis is thought to be immunopathology and epithelioid cell granuloma formation is considered to be expression of protective immunity. Recently roles of cytokines for granuloma formation are gradually elucidated. In this symposium, mechanisms and functions of necrosis and granuloma formation Dr. Akagawa reported differentiation of two types of phenotypically different macrophages from human monocytes by GM (granulocyte-macrophage)-CSF or M (macrophage)-CSF. Interestingly such a basic differentiation induced by CSF was affected by IL-4 (interleukin-4). Langerhans-like dendritic cells were generated by cooperation of GM-CSF and IL-4, and multinucleated cells were generated by cooperation of IL-4 and M-CSF. Dr. Fukuda reported human Langerhans cell granulomatosis (LCG) from the pathological and immunohistochemical standpoints. In situ proliferation of LCs in the LCG was demonstrated by immunohistochemistry using antibody to PCNA (proliferating cell nuclear antigen) which is used to detect proliferating cells. In the course of granuloma formation, damage and disruption of lung structure such as alveolar basement membrane and elastic tissue framework, and reactive intraluminar fibrosis was observed. Mechanism of cystic dilation was also reported. Cytokines might play important roles in these events. Dr. Ina demonstrated experimental epithelioid cell granuloma formation. Extract (granuloma inducing factor, GIF) from Schistosoma mansoni Egg-induced granuloma, TNF -alpha, or IL-1 beta were coated, individually on the surface of beads, then these beads were inoculated to rat's skins or cultured with rat's monocytes. Four weeks later, epithelioid cell granuloma was demonstrated histologically and electronmicroscopically around beads in vitro and in vivo. GIF-induced granuloma was more organized than cytokine-induced ones. In vitro using human monocytes, activated macrophages accumulated around beads of which cytokines or GIF were coated. It was suspected that many cytokines or other factors are needed to make epithelioid cell granuloma. Dr. Sakamoto showed the presence of acid fast bacilli and various inflammatory cells including lymphocytes and macrophages in the tuberculous caseous necrosis after exudative reaction (E-necrosis) by immunohistochemistry. But no acid fast bacilli or inflammatory cells were found in the caseous necrosis after productive reaction (P-necrosis). TNF-alpha (tumor necrosis factor-alpha) and IL-4 were stained in the E-necrosis and IL-4 and ICAM-1 (intercellular adhesion molecule-1) were positively stained in the cytoplasm of epithelioid cells by immunohistochemistry. It was suspected that many cells and cytokines were involved in epithelioid cell granuloma formation and caseous necrosis formation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[The 69th annual meeting symposium. II: Mechanism of necrotizing granuloma formation and its function]. 779 74

Cytokines and chemokines determine mobilisation of Langerhans cells and their dysregulation is implicated in the pathogenesis of Langerhans cell histiocytosis (LCH). Twenty point mutations of 12 different cytokine genes were studied in 41 Italian children, 15 with single-system (SS) and 26 with multi-system disease. The allele and genotype distributions of interleukin-4 (IL-4) and interferon-gamma (IFNgamma) were significantly different in patients vs. 140 controls (P = 0.007, and P = 0.018). Older children with single-system disease shared the 'anti-inflammatory profile' determined by the intermediate producer genotype IFNgamma +874A/T (P = 0.029) and the high-producer genotypes IL-4 -590C/T and T/T (P = 0.029). Our findings suggest that specific cytokine gene variants affect susceptibility to LCH and its clinical heterogeneity.
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PMID:Specific polymorphisms of cytokine genes are associated with different risks to develop single-system or multi-system childhood Langerhans cell histiocytosis. 1648 80