A mannose-binding receptor is expressed on human keratinocytes and mediates killing of Candida albicans.
Human keratinocytes are known to kill Candida albicans in vitro, but the mechanism of killing is not yet understood. Here, we demonstrate that spontaneous, ultraviolet-B-light-induced, alpha-melanocyte-stimulating-hormone-induced, and interleukin-8-induced Candida killing by keratinocytes can be inhibited with mannan and mannosylated bovine serum albumin (Man-BSA). A polyclonal goat serum raised against the human macrophage mannose receptor stained suprabasal keratinocytes, but no staining was observed on keratinocytes with a monoclonal antibody (mAb15) specific for the human macrophage mannose receptor. Mannose-affinity chromatography of keratinocyte extract isolated a 200 kDa protein, and on the Western blot the goat antiserum reacted with a 200 kDa protein. In radioligand binding studies, the binding of 125I-Man-BSA to human keratinocytes was inhibited by mannan in a concentration-dependent manner. Analysis of the binding revealed a single class keratinocyte mannose receptor with a KD of 1.4 x 10(-8) M and a Bmax of 1 x 10(4) binding sites per cell. The binding of 125I-Man- BSA to keratinocytes proved to be time-dependent, acid-precipitable, and Ca2+- and trypsin-sensitive. After trypsinization the receptors underwent a rapid recovery at 37 degrees C. These results demonstrate the presence of mannose receptor on human keratinocytes, and its active involvement in the killing of Candida albicans.
Szolnoky
G
G
Department of Dermatology, Albert Szent-Györgyi Medical Center, University of Szeged, Szeged, Hungary. szolnoky@derma.u-szeged.hu
Bata-Csörgö
Z
Z
Kenderessy
A S
AS
Kiss
M
M
Pivarcsi
A
A
Novák
Z
Z
Nagy Newman
K
K
Michel
G
G
Ruzicka
T
T
Maródi
L
L
Dobozy
A
A
Kemény
L
L
D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology* / Q000378:metabolism; D002448:Cell Adhesion; D002614:Chelating Agents / Q000494:pharmacology; D003429:Cross Reactions; D004533:Egtazic Acid / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology*; D037181:Lectins, C-Type; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008351:Mannans / Q000494:pharmacology; D008358:Mannose / Q000493:pharmacokinetics; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D012709:Serum Albumin / Q000493:pharmacokinetics; D012867:Skin / Q000166:cytology / Q000382:microbiology
D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D007457:Iodine Radioisotopes; D037181:Lectins, C-Type; D008351:Mannans; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D012709:Serum Albumin; C023840:mannose-bovine serum albumin conjugate; D004533:Egtazic Acid; D008358:Mannose; D002118:Calcium