Protein kinase C transduces the signal for Langerhans' cell migration from the epidermis.
Langerhans' cells (LC) take up antigen in the epidermis and then migrate to the local lymph nodes where they present the antigen to T lymphocytes, initiating cutaneous immune responses. However the intracellular mechanisms which mediate LC migration from the epidermis are unknown. We have demonstrated that activation of protein kinase C (PKC) induces this LC migration. An analogue of diacylglycerol (DAG), the physiological activator of PKC, L-alpha-dioctanoyl glycerol (oDAG), applied topically onto the skin of mice caused a significant depletion in the density of Ia+ and J11d+ epidermal LC. oDAG decreased the density of LC in both BALB/c and C57BL mice 24 hr following application, over a dose range of 0.5-24 microM; 200 or 0.05 microM being ineffective. LC density remained depressed for up to 7 days and oDAG increased the number of fluorescein isothiocyanate (FITC) positive cells in the local lymph nodes of mice treated topically with FITC, indicating that oDAG induced LC migration from the epidermis. Additionally, LC migration from the epidermis induced by the contact sensitizer 2,4,6-trinitrochlorobenzene (TNCB) was blocked when PKC was inhibited by palmitoyl-DL-carnitine chloride (PCC) or D-Sphingosine (Sph), indicating that LC cannot migrate from the epidermis when PKC is inhibited. However, PCC did not inhibit the induction of contact sensitivity. Thus PKC transduces the signal which leads to LC migration from the epidermis, and disruptions in this secondary messenger may interfere with the induction of immune responses in the skin by disturbing LC migration from the epidermis to the local lymph nodes.
Halliday
G M
GM
Department of Dermatology, University of Sydney, Royal Prince Alfred Hospital, NSW, Australia.
Lucas
A D
AD
D000287:Administration, Topical; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology; D004075:Diglycerides / Q000008:administration & dosage* / Q000276:immunology; D004817:Epidermis / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010172:Palmitoylcarnitine / Q000276:immunology; D010853:Picryl Chloride / Q000276:immunology; D011493:Protein Kinase C / Q000276:immunology*
D004075:Diglycerides; C044295:1,2-dioctanoylglycerol; D010172:Palmitoylcarnitine; D011493:Protein Kinase C; D010853:Picryl Chloride