Characterization of a new amino acid transport system in human epidermal Langerhans cells

University dissertation from Department of Dermatology and Venereology (Lund)

Abstract: Based on the discovery of a new amino acid transport system in Langerhans cells (LC), various aspects concerning the L-dopa uptake mechanism into human epidermal LC and the energy metabolism of epidermis have been examined and subsequently characterised. The system lacks any characteristics of other described amino acid transport systems in other cell types. The Falck/Hillarp histofluorescence method was used, studying uptake in individual LC in situ in their microenvironment. For the first time, experiments showed that, despite the formal presence of mitochondria, the human epidermis is capable of an aerobic lactate production, probably dependent on a disturbed Pasteur effect. It was also proved that human epidermis has a lower energy charge value than other body cells, apart from smooth muscle cells. Increased lactate production in epidermis, which can be inhibited by iodoacetate, implies an increased intracellular proton production. The energetics of the L-dopa transport into LC is probably a countertransport (antiport) of protons due to aerobic production of lactate. Further experiments showed that L-dopa can be dislocated out of LC by certain amino acids on the outside of the cells, either acting in a trans-stimulatory fashion or by exchanging with intracellular L-dopa, getting “useful” amino acids into the cells. This, now extracellular L-dopa, can begin a new in- and out-transport cycle. Using a H+,K+-ATPase-inhibitor (omeprazole and some analogues), experiments showed that most of these inhibit the L-dopa transport into LC, probably not caused by affecting a thiol group essential for this transport. The actual mechanism is unknown.

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