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001-es BibID:	BIBFORM033821
035-os BibID:	(WoS)000300876300003 (Scopus)84857734407
Első szerző:	Tsakiris, Ioannis (orvos)
Cím:	Carboxypeptidase-M is regulated by lipids and CSFs in macrophages and dendritic cells and expressed selectively in tissue granulomas and foam cells / Tsakiris I., Torocsik D., Gyongyosi A., Dozsa A., Szatmari I., Szanto A., Soos G., Nemes Z., Igali L., Marton I., Takats Z., Nagy L., Dezso B.
Dátum:	2012
ISSN:	0023-6837
Megjegyzések:	Granulomatous inflammations, characterized by the presence of activated macrophages (MAs) forming epithelioid cell (EPC) clusters, are usually easy to recognize. However, in ambiguous cases the use of a MA marker that expresses selectively in EPCs may be needed. Here, we report that carboxypeptidase-M (CPM), a MA-differentiation marker, is preferentially induced in EPCs of all granuloma types studied, but not in resting MAs. As CPM is not expressed constitutively in MAs, this allows utilization of CPM-immunohistochemistry in diagnostics of minute granuloma detection when dense non-granulomatous MAs are also present. Despite this rule, hardly any detectable CPM was found in advanced/active tubercle caseous disease, albeit in early tuberculosis granuloma, MAs still expressed CPM. Indeed, in vitro both the CPM-protein and -mRNA became downregulated when MAs were infected with live mycobacteria. In vitro, MA-CPM transcript is neither induced remarkably by interferon-γ, known to cause classical MA activation, nor by IL-4, an alternative MA activator. Instead, CPM is selectively expressed in lipid-laden MAs, including the foam cells of atherosclerotic plaques, xanthomatous lesions and lipid pneumonias. By using serum, rich in lipids, and low-density lipoprotein (LDL) or VLDL, CPM upregulation could be reproduced in vitro in monocyte-derived MAs both at transcriptional and protein levels, and the increase is repressed under lipid-depleted conditions. The microarray analyses support the notion that CPM induction correlates with a robust progressive increase in CPM gene expression during monocyte to MA maturation and dendritic cell (DC) differentiation mediated by granulocyte-MA-colony-stimulating factor+IL-4. M-CSF alone also induced CPM. These results collectively indicate that CPM upregulation in MAs is preferentially associated with increased lipid uptake, and exposure to CSF, features of EPCs, also. Therefore, CPM-immunohistochemistry is useful for granuloma and foam MA detections in tissue sections. Furthermore, the present data offer CPM for the first time to be a novel marker and cellular player in lipid uptake and/or metabolism of MAs by promoting foam cell formation.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk open access article
Megjelenés:	Laboratory Investigation. - 92 : 3 (2012), p. 345-361. -
További szerzők:	Töröcsik Dániel (1979-) (bőrgyógyász) Gyöngyösi Adrienn (1982-) (biológus) Dózsa Anikó (1978-) (Ph.D hallgató, orvos) Szatmári István (1971-) (biológus) Szántó Attila (1976-) (orvos, biokémikus) Soós Györgyike (1959-) (pathológus) Nemes Zoltán (1942-) (patológus) Igali László Márton Ildikó (1954-) (fogszakorvos) Takáts Zoltán Nagy László (1966-) (molekuláris sejtbiológus, biokémikus) Dezső Balázs (1951-) (pathológus)
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	bibEBI12844
Első szerző:	Vályi-Nagy István
Cím:	Undifferentiated keratinocytes control growth, morphology, and antigen expression of normal melanocytes through cell-cell contact / Vályi-Nagy, I. T. , Hirka, G., Jensen, P. J., Shih, I. M., Juhász, I., Herlyn, M.
Dátum:	1993
ISSN:	0023-6837 1530-0307
Megjegyzések:	BACKGROUND: Melanocytes in the normal human epidermis are generally dendritic and neither proliferate nor express melanoma-associated antigens. In culture, on the other hand, melanocytes are bi- to tripolar, proliferate with 2 to 4 day doubling times, and express melanoma-associated antigens. This observation prompted us to investigate the regulatory role of keratinocytes for growth, morphology, and antigen expression of melanocytes. EXPERIMENTAL DESIGN: Melanocytes and keratinocytes were cultured under three different co-culture conditions: (a) separated by a semiporous membrane, (b) in monolayer cultures allowing direct contact between cells, and (c) in three-dimensional epidermal reconstructs. RESULTS: Melanocytes separated from keratinocytes by semiporous membranes remained di- and tripolar and could not proliferate in medium optimal for keratinocytes. When cell-cell contact was established between melanocytes and undifferentiated, but not differentiated, keratinocytes, melanocytes proliferated at a rate similar to keratinocytes and they developed multiple dendrites. In co-cultures allowing the multi-layered growth of keratinocytes, melanocytes were nonproliferative when juxtaposed to undifferentiated keratinocytes in the basal layer, but proliferated when surrounded by differentiated keratinocytes in the intermediate and upper layers. Expression of melanoma-associated antigens on melanocytes decreased to similar levels as in normal skin when melanocytes were in direct contact with undifferentiated, but not differentiated, keratinocytes. CONCLUSIONS: Undifferentiated, but not differentiated, keratinocytes control growth, morphology, and antigen expression of melanocytes through direct cell-cell contact. These results suggest that the phenotypic characteristics of nevus and melanoma cells in the dermis, i.e., proliferation and expression of tumor-associated antigens, may be due to their loss of contact with undifferentiation keratinocytes.
Tárgyszavak:	idegen nyelvű folyóiratközlemény külföldi lapban külföldön készült közlemény
Megjelenés:	Laboratory Investigation. - 69 : 2 (1993), p. 152-159. -
További szerzők:	Hirka G. Jensen, P. J. Shih, Ie-Ming Juhász István (1956-) (bőrgyógyász, bőrsebész, kozmetológus, klinikai onkológus) Herlyn, Meenhard
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