Decreased level of prosaposin in atopic skin.
In the skin of atopic dermatitis patients, the amount of ceramides in the stratum corneum is decreased. Although the cause of this decrease may be due to the higher activity of acylase, a decrease in the activity of sphingolipid activator proteins may also be the cause. A polyclonal antibody to saposin D, elicited by immunizing rabbits with the synthetic polypeptide from cDNA of saposin D, cross-reacted with a single 65-kDa epidermal protein of pI 5.6 in a 2-dimensional immunoblot study, suggesting that it was prosaposin, the precursor protein of saposin D, from its molecular weight and demonstrating its immunohistochemical localization in the innermost cell layers of the stratum corneum of the skin. The antigenic material was also observed in the epithelium of the esophagus, pneumocytes of the lungs, hepatocytes, and glandular cells of the stomach. Immunoelectron microscopy showed the antigenic material in the cytoplasm of the granular cells and the intercellular spaces, either between the stratum granulosum and the stratum corneum or on the stratum corneum cell envelope. By ELISA, the amount of the 65-kDa protein in the inner surface skin of the upper arm of atopic dermatitis patients (nonlesional skin) [4.1 +/- 2.0 microg per 7 mm2 (mean +/- SD), n = 10] was found to be significantly decreased (p < 0.05) to 66% of that in the normal control (6.2 +/- 1.5 microg per 7 mm2, n = 10). Therefore, the suppression of prosaposin synthesis may be related to the abnormal stratum corneum formation in atopic skin through lower activation of glucosylcerebrosidase or sphingomyelinase.
Cui
C Y
CY
Department of Dermatology, Kinki University School of Medicine, Osaka, Japan.
Kusuda
S
S
Seguchi
T
T
Takahashi
M
M
Aisu
K
K
Tezuka
T
T
D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D000906:Antibodies / Q000032:analysis; D000937:Antigen-Antibody Reactions; D002462:Cell Membrane / Q000737:chemistry; D055572:Ceramidases; D003593:Cytoplasm / Q000737:chemistry; D003876:Dermatitis, Atopic / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005962:Glucosylceramidase / Q000037:antagonists & inhibitors; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016253:Microscopy, Immunoelectron; D011498:Protein Precursors / Q000378:metabolism; D049231:Saposins; D012867:Skin / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure
D000906:Antibodies; D006023:Glycoproteins; C483345:PSAP protein, human; D011498:Protein Precursors; D049231:Saposins; D005962:Glucosylceramidase; D000581:Amidohydrolases; D055572:Ceramidases