LEKTI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum.
Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is a putative serine protease inhibitor encoded by serine protease inhibitor Kazal-type 5 (SPINK5). It is strongly expressed in differentiated keratinocytes in normal skin but expression is markedly reduced or absent in Netherton syndrome (NS), a severe ichthyosis caused by SPINK5 mutations. At present, however, both the precise intracellular localization and biological roles of LEKTI are not known. To understand the functional role of LEKTI, we examined the localization of LEKTI together with kallikrein (KLK)7 and KLK5, possible targets of LEKTI, in the human epidermis, by confocal laser scanning microscopy and immunoelectron microscopy. In normal skin, LEKTI, KLK7, and KLK5 were all found in the lamellar granule (LG) system, but were separately localized. LEKTI was expressed earlier than KLK7 and KLK5. In NS skin, LEKTI was absent and an abnormal split in the superficial stratum granulosum was seen in three of four cases. Collectively, these results suggest that in normal skin the LG system transports and secretes LEKTI earlier than KLK7 and KLK5 preventing premature loss of stratum corneum integrity/cohesion. Our data provide new insights into the biological functions of LG and the pathogenesis of NS.
Ishida-Yamamoto
Akemi
A
Department of Dermatology, Asahikawa Medical College, Midorigaoka-Higashi 2-1-1-1, Asahikawa 078-8510, Japan. akemi@asahikawa-med.ac.jp
Deraison
Céline
C
Bonnart
Chrystelle
C
Bitoun
Emmanuelle
E
Robinson
Ross
R
O'Brien
Timothy J
TJ
Wakamatsu
Kotaro
K
Ohtsubo
Sawa
S
Takahashi
Hidetoshi
H
Hashimoto
Yoshio
Y
Dopping-Hepenstal
Patricia J C
PJ
McGrath
John A
JA
Iizuka
Hajime
H
Richard
Gabriele
G
Hovnanian
Alain
A
D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003896:Desmosomes / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006801:Humans; D007057:Ichthyosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D007610:Kallikreins; D015603:Keratinocytes / Q000201:enzymology / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D053491:Proteinase Inhibitory Proteins, Secretory; D012697:Serine Endopeptidases / Q000378:metabolism*; D000074163:Serine Peptidase Inhibitor Kazal-Type 5
D002352:Carrier Proteins; D053491:Proteinase Inhibitory Proteins, Secretory; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; C400147:KLK5 protein, human; C082472:KLK7 protein, human; D007610:Kallikreins; D012697:Serine Endopeptidases