title: Cellular changes that accompany shedding of human corneocytes.
abstract: Corneocyte desquamation has been ascribed to the following: 1) proteolytic degradation of corneodesmosomes (CDs); 2) disorganization of extracellular lamellar bilayers; and/or 3) "swell-shrinkage-slough" from hydration/dehydration. To address the cellular basis for normal exfoliation, we compared changes in lamellar bilayer architecture and CD structure in D-Squame strips from the first versus fifth stripping ("outer" vs. "mid"-stratum corneum (SC), respectively) from nine normal adult forearms. Strippings were either processed for standard electron microscopy (EM) or for ruthenium-, or osmium-tetroxide vapor fixation, followed by immediate epoxy embedment, an artifact-free protocol, which, to our knowledge, is previously unreported. CDs are largely intact in the mid-SC, but replaced by electron-dense (hydrophilic) clefts (lacunae) that expand laterally, splitting lamellar arrays in the outer SC. Some undegraded desmoglein 1/desmocollin 1 redistribute uniformly into corneocyte envelopes (CEs) in the outer SC (shown by proteomics, Z-stack confocal imaging, and immunoEM). CEs then thicken, likely facilitating exfoliation by increasing corneocyte rigidity. In vapor-fixed images, hydration only altered the volume of the extracellular compartment, expanding lacunae, further separating membrane arrays. During dehydration, air replaced water, maintaining the expanded extracellular compartment. Hydration also provoked degradation of membranes by activating contiguous acidic ceramidase activity. Together, these studies identify several parallel mechanisms that orchestrate exfoliation from the surface of normal human skin.
authors: Department of Veterans Affairs Medical Center and Department of Dermatology, Dermatology Service, University of California, San Francisco, San Francisco, California, USA; Department of Dermatology, National Cheng Kung University Hospital, and Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors: Tzu-Kai
authors: TK
authors: Lin
authors: Department of Veterans Affairs Medical Center and Department of Dermatology, Dermatology Service, University of California, San Francisco, San Francisco, California, USA.
authors: Debra
authors: D
authors: Crumrine
authors: Department of Veterans Affairs Medical Center and Department of Dermatology, Dermatology Service, University of California, San Francisco, San Francisco, California, USA.
authors: Larry D
authors: LD
authors: Ackerman
authors: Department of Veterans Affairs Medical Center and Department of Dermatology, Dermatology Service, University of California, San Francisco, San Francisco, California, USA; Department of Dermatology, Hospital General de Ciudad Real, Universidad de Castilla-La Mancha, Ciudad Real, Spain.
authors: Juan-Luis
authors: JL
authors: Santiago
authors: Department of Veterans Affairs Medical Center and Department of Dermatology, Dermatology Service, University of California, San Francisco, San Francisco, California, USA; Department of Dermatology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels, Belgium.
authors: Truus
authors: T
authors: Roelandt
authors: Department of Veterans Affairs Medical Center and Department of Dermatology, Dermatology Service, University of California, San Francisco, San Francisco, California, USA.
authors: Yoshikazu
authors: Y
authors: Uchida
authors: Department of Veterans Affairs Medical Center and Department of Dermatology, Dermatology Service, University of California, San Francisco, San Francisco, California, USA.
authors: Melanie
authors: M
authors: Hupe
authors: Department of Biomedicinal Chemistry, Institut de Química Avançada de Catalunya, CSIC, Barcelona, Spain.
authors: Gemma
authors: G
authors: Fabriàs
authors: Department of Biomedicinal Chemistry, Institut de Química Avançada de Catalunya, CSIC, Barcelona, Spain.
authors: Jose L
authors: JL
authors: Abad
authors: Department of Environmental Toxicology, University of California, Davis, Davis, California, USA.
authors: Robert H
authors: RH
authors: Rice
authors: Department of Veterans Affairs Medical Center and Department of Dermatology, Dermatology Service, University of California, San Francisco, San Francisco, California, USA. Electronic address: eliasp@derm.ucsf.edu.
authors: Peter M
authors: PM
authors: Elias
mesh_terms: D000328:Adult; D003681:Dehydration / Q000378:metabolism / Q000473:pathology; D051187:Desmocollins / Q000378:metabolism; D051183:Desmoglein 1 / Q000378:metabolism; D003896:Desmosomes / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D004817:Epidermis / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure*; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure*; D005404:Fixatives; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008854:Microscopy, Electron
chemical_list: C109656:CDSN protein, human; C081560:DSC1 protein, human; D051187:Desmocollins; D051183:Desmoglein 1; D005404:Fixatives; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins