CD2-mediated CD59 stimulation in keratinocytes results in secretion of IL-1alpha, IL-6, and GM-CSF: implications for the interaction of keratinocytes with intraepidermal T lymphocytes.
Normal epidermal keratinocytes are here shown to express membrane-associated complement inhibitory protein CD59 in vitro that protects keratinocytes from damage by complement because preincubation with blocking antibodies to CD59 renders the cells susceptible to complement mediated lysis. CD59 expression in keratinocytes is constitutive and not modulated by inflammatory cytokines, phorbol myristate acetate (PMA), and a number of other agents tested. Antibody mediated cross-linking of CD59, however, revealed an additional function of CD59: keratinocytes in vitro are activated to secrete the cytokines IL-1alpha, IL-6, and GM-CSF. CD59 mediated induction of these cytokines is regulated at the transcriptional level. Binding of keratinocytes to HL60 cells that express CD59 ligand CD2 induced the same pattern of secreted cytokines whereas binding to CD2-negative HL60 cells did not. Induction of cytokine secretion was completely blocked by preincubation of keratinocytes with both anti-CD58 and anti-CD59 antibodies together. The results demonstrate that CD2-mediated CD59 stimulation in human keratinocytes leads to synthesis of a particular set of cytokines implying a potential activation pathway in the interaction of keratinocytes with intraepithelial CD2+ T cells.
Naderi
S
S
Department of Dermatology, University of Bonn, Bonn, Germany.
Hofmann
P
P
Seiter
S
S
Tilgen
W
W
Abken
H
H
Reinhold
U
U
D019138:Antibodies, Blocking / Q000378:metabolism; D018801:CD2 Antigens / Q000235:genetics / Q000502:physiology*; D018968:CD58 Antigens / Q000276:immunology / Q000378:metabolism; D018957:CD59 Antigens / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D003165:Complement System Proteins / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D020014:K562 Cells; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
D019138:Antibodies, Blocking; D018801:CD2 Antigens; D018968:CD58 Antigens; D018957:CD59 Antigens; D007375:Interleukin-1; D015850:Interleukin-6; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003165:Complement System Proteins; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase