title: Pemphigus vulgaris: accumulation of apoptotic cells in dermis and epidermis possibly relates to pathophysiology through TNF-alpha production by phagocytes.
abstract: Apoptotic cells are present in the epidermis of pemphigus vulgaris (PV) patients and their accumulation has been linked to chronic inflammatory disorders. TNF-α is elevated in sera of PV patients and has only been detected in acantholytic and periacantholytic keratinocytes (KC), therefore another TNF-α source might exist. We analyzed, in lesional and perilesional skin of 5 active untreated PV patients, the presence of apoptotic cells, TNF-α and phagocytic infiltrate. In vitro, we analyzed whether phagocytosis of apoptotic KCs by monocytes causes TNF-α release. We found a significant increase of apoptotic cells in the epidermis and dermis of PV patients, by TUNEL, and activated caspase-3. TNF-α was present in the skin of PV patients, especially in the dermis. Phagocytic CD14+ cells were increased, mostly in the dermis of PV patients. In vitro phagocytosis of apoptotic KCs by monocytes caused enhanced TNF-α production, which correlated with the number of apoptotic KCs in the co-culture. Thus, accumulation of apoptotic cells in PV could promote TNF-α production by monocytes, which could, in turn, cause further apoptosis, closing a vicious circle.
authors.affiliation: Departamento de Medicina Experimental, Servicio de Dermatología, Universidad Nacional Autónoma de México, Dr. Balmis 148, México D.F. 06726.
authors.forename: Mariana
authors.initials: M
authors.lastname: Chiapa-Labastida
authors.forename: Alejandro
authors.initials: A
authors.lastname: Zentella-Dehesa
authors.forename: Gladys
authors.initials: G
authors.lastname: León-Dorantes
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Becker
mesh_terms: D016475:3T3 Cells; D000328:Adult; D000818:Animals; D020405:Dermis / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D015603:Keratinocytes / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D010392:Pemphigus / Q000503:physiopathology*; D010586:Phagocytes / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha