Corneocyte Desquamation Research Articles

Development and organization of human stratum corneum after birth: electron microscopy isotropy score and immunocytochemical corneocyte labelling as epidermal maturation's markers in infancy

There is growing evidence for the ongoing structural and functional adaptation of the skin after birth. The aim of this study was the definition of scanning electron microscopy markers of skin maturation in different age groups (birth to adulthood). We propose a semiquantitative score to analyse the maturation of the skin surface and a complementary evaluation of the distribution of corneodesmosin and corneodesmosomes. An electron microscopy isotropy (E.M.I.) score was performed in six age-groups to include fullterm neonates, babies, children and adults. The distribution of corneodesmosome remnants was analysed by corneodesmosin distribution with immunocytochemical corneocyte labelling. The E.M.I. score showed the highest anisotropy in neonates. The youngest groups displayed irregular and thick cell clusters composed of poorly individualized cells. In the older groups, the distribution of superficial corneocytes was more regular. The cells evenly covered the surface and displayed easily visualized single cell outlines. The distribution of immune-labelled corneodesmosome remnants and the corneocyte projected area showed a correlation between age and structural maturation. The observed evolution indicated a poorly controlled process of corneocyte desquamation in infants and confirmed the relative immaturity of the epidermal barrier up to 1-2 years after birth under basal conditions. Our study is the first attempt at semiquantitative evaluation of the micromorphology maturation of the epidermal surface at the ultrastructural level. The E.M.I. score and the associated pattern of corneodesmosome breakdown may be used as markers of the stratum corneum maturation.

Keratinocyte-Specific Mesotrypsin Contributes to the Desquamation Process via Kallikrein Activation and LEKTI Degradation

Kallikrein-related peptidases (KLKs) have critical roles in corneocyte desquamation and are regulated by lymphoepithelial Kazal-type inhibitor (LEKTI). However, it is unclear how these proteases are activated and how activated KLKs are released from LEKTI in the upper cornified layer. Recently, we reported cloning of a PRSS3 gene product, keratinocyte-specific mesotrypsin, from a cDNA library. We hypothesized that mesotrypsin is involved in the desquamation process, and the aim of the present study was to test this idea by examining the effects of mesotrypsin on representative desquamation-related enzymes pro-KLK5 and pro-KLK7. Incubation of mesotrypsin and these zymogens resulted in generation of the active forms. KLK activities were effectively inhibited by recombinant LEKTI domains D2, D2-5, D2-6, D2-7, D5, D6, D6-9, D7, D7-9, and D10-15, whereas mesotrypsin activity was not susceptible to these domains, and in fact degraded them. Immunoelectron microscopy demonstrated that mesotrypsin was localized in the cytoplasm of granular cells and intercellular spaces of the cornified layer. Proximity ligation assay showed close association between mesotrypsin and KLKs in the granular to cornified layers. Age-dependency analysis revealed that mesotrypsin was markedly downregulated in corneocyte extract from donors in their sixties, compared with younger donors. Collectively, our findings suggest that mesotrypsin contributes to the desquamation process by activating KLKs and degrading the intrinsic KLKs' inhibitor LEKTI.

Cellular Changes that Accompany Shedding of Human Corneocytes

Corneocyte desquamation has been ascribed to either: 1) proteolytic degradation of corneodesmosomes (CD); 2) disorganization of extracellular lamellar bilayers; and/or 3) ‘swell-shrinkage-slough’ (SSS) from hydration/dehydration. To address the cellular basis for normal exfoliation, we compared changes in lamellar bilayer architecture and CD structure in DSquame® strips from the 1st vs. 5th stripping (‘outer’ vs. ‘mid’-stratum corneum [SC], respectively) from 9 normal adult forearms. Strippings were either processed for standard EM or for ruthenium (Ru-V)- or osmium-tetroxide (Os-V) vapor fixation, followed by immediate epoxy embedment, an artifact-free protocol that 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 DSG1/DSC1 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.

Circumscribed palmo‐plantar hypokeratosis: a disease of desquamation? Immunohistological study of five cases and literature review

Circumscribed palmoplantar hypokeratosis (CPH) is a recently recognized, rarely reported dermatosis that shows characteristic clinicopathological features; however, its pathogenesis remains unknown. The aim of this study was to get further insight into the pathogenesis of CPH. An immunohistological study was performed on five cases of CPH to investigate the expression of several epidermal proliferation and differentiation proteins, with emphasis on those involved in corneocyte desquamation [including corneodesmosin, kallikrein 5 and lympho-epithelial Kazal type inhibitor (LEKTI)]. In three of five cases, a decreased expression of LEKTI, corneodesmosin and filaggrin was found, along with an increased expression of kallikrein 5 and keratin 6. The expression of several other antigens (including involucrin, Ki67, p63, CD138/syndecan I, EGF-R) did not present a consistently different pattern as compared with the unaffected epidermis. The immunohistopathologic features of CPH suggest that an altered (accelerated) corneocyte desquamation process could be the main pathological mechanism underlying the development of lesions.

Role of Tissue-Type Plasminogen Activator in Salicylic Acid–Induced Sloughing of Human Corn Tissue

Plasminogen activators (PAs) and their regulatory counterparts, PA inhibitors (PAIs), play a role in normal differentiation processes and various pathophysiologic conditions of the epidermis. Normal desquamation of corneocytes from the skin3s surface may, in part, be regulated by the balanced activities of tissue-type PA (tPA) and PAI-2. Salicylic acid (SA) is commonly used to remove the hyperkeratotic tissue of corns, calluses, and verrucae, and it may disrupt intercellular adhesion structures; however, its exact mechanism of keratolytic action is poorly defined. We sought to determine the effects of SA by comparing the levels of PA and PAI messenger RNA (mRNA) in normal skin, untreated corns, and SA-treated corns. Untreated and SA-treated human corn tissue samples were obtained from patients electing surgery to repair bony defects that underlay their lesions. Histopathologic examination of corns was performed by staining the tissue sections with hematoxylin and eosin and by light microscopy. Polymerase chain reaction was used to compare mRNA expression of PAs and PAIs in normal skin, untreated corns, and SA-treated corns. We demonstrated lower tPA and higher PAI-2 mRNA levels in corn tissue compared with normal skin. In corn tissue treated with SA, the expression of tPA mRNA increased and of PAI-2 mRNA decreased to the levels found in normal skin. An altered balance in tPA and PAI-2 levels contributes to the induction of hyperkeratotic corn tissue and suggests that the keratolytic action of SA is associated with its ability to stimulate proteinase-meditated desquamation processes.

A potential role for tissue kallikrein-related peptidases in human cervico-vaginal physiology

Human tissue kallikrein-related peptidases (KLK) are a family of 15 genes located on chromosome 19q13.4 that encode secreted serine proteases with trypsin- and/or chymotrypsin-like activity. Relatively large levels of many KLKs are present in human cervico-vaginal fluid (CVF) and in the supernatant of cultured human vaginal epithelial cells. Many KLKs are also hormonally regulated in vaginal epithelial cells, particularly by glucocorticoids and estrogens. The physiological role of KLK in the vagina is currently unknown; however, analysis of the CVF proteome has revealed clues for potential KLK functions in this environment. Here, we detail potential roles for KLKs in cervico-vaginal physiology. First, we suggest that KLKs play a role in the vagina similar to their role in skin physiology: (1) in the desquamation of vaginal epithelial cells, similar to their activity in the desquamation of skin corneocytes; and (2) in their ability to activate antimicrobial proteins in CVF as they do in sweat. Consequently, we hypothesize that dysregulated KLK expression in the vagina could lead to the development of pathological conditions such as desquamative inflammatory vaginitis. Second, we propose that KLKs may play a role in premature rupture of membranes and pre-term birth through their cleavage of fetal membrane extracellular matrix proteins.

The biology of vernix caseosa

The biology and physical properties of the uniquely human skin cream 'vernix caseosa' are discussed. This material coats the foetal skin surface during the last trimester of gestation and provides multiple beneficial functions for the foetus and newborn infant. Vernix has a complex structure similar to stratum corneum but lacks lipid lamellae and is more plastic due to the absence of desmosomal constraints. In utero, vernix is made in part by foetal sebaceous glands, interacts with pulmonary surfactant, detaches into the amniotic fluid, and is swallowed by the foetus. At the time of birth, vernix has a remarkably constant water content approximating 80%. Postnatally, vernix is simultaneously a cleanser, a moisturizer, an anti-infective, and an anti-oxidant. Vernix facilitates acid mantle development and supports normal bacterial colonization. Its hydrated cellular structure and unusual lipid composition provide a 'best' solution for the needs of the foetus and newborn, not least of which is the attraction of caregivers. Vernix is an important natural biomaterial of potential interest to cosmetic scientists, and other disciplines involved in product development and therapies targeting the complex interface between the stratum corneum and a changing terrestrial environment.

LXR and PPAR activators stimulate cholesterol sulfotransferase type 2 isoform 1b in human keratinocytes

Liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs) are potent regulators of keratinocyte proliferation, differentiation, and epidermal permeability barrier homeostasis. Cholesterol sulfotransferase type 2B isoform 1b (SULT2B1b) is a key enzyme in the synthesis of cholesterol sulfate (CS), a critical regulator of keratinocyte differentiation and desquamation, as well as a mediator of barrier homeostasis. In this study, we assessed the effect of activators of LXR, PPARalpha, PPARbeta/delta, and PPARgamma on SULT2B1b gene expression and enzyme activity in cultured human keratinocytes (CHKs). Our results demonstrate that PPAR and LXR activators increase SULT2B1b mRNA levels, with the most dramatic effect (a 26-fold increase) induced by the PPARgamma activator ciglitazone. Ciglitazone upregulates SULT2B1b mRNA in a dose- and time-dependent manner. Moreover, the stimulation of SULT2B1b gene expression by LXR and PPAR activators occurs in both undifferentiated and differentiated CHKs. The upregulation of SULT2B1b mRNA by ciglitazone appears to occur at a transcriptional level, because the degradation of SULT2B1b is not accelerated by ciglitazone. In addition, cycloheximide almost completely blocks the ciglitazone-induced increase in SULT2B1b mRNA, suggesting that the transcription of SULTB1b mRNA is dependent on new protein synthesis. Finally, LXR and PPAR activators also increased the activity of cholesterol sulfotransferase. Thus, LXR and PPAR activators regulate the expression of SULT2B1b, the key enzyme in the synthesis of CS, which is a potent regulator of epidermal differentiation and corneocyte desquamation.

Multiple tissue kallikrein mRNA and protein expression in normal skin and skin diseases

Human tissue kallikreins are a gene family (KLK1-KLK15) encoding for 15 secretory serine proteases (hK1-hK15). Two tissue kallikrein proteins, hK5 and hK7, were previously found in the stratum corneum (SC), stratum granulosum (SG) and appendages. hK8 was also shown to be secreted via lamellar granules and numerous KLK mRNAs were previously identified. KLKs are believed to be responsible for desquamation of corneocytes and sebum, sweat and hair maturation. To demonstrate immunohistochemically the expression of hK6, hK8 and hK13 in normal skin tissue and to show an increased cell number expressing kallikrein mRNAs and proteins in psoriasis vulgaris (PV) and atopic dermatitis (AD). Samples of normal, PV and AD skin were obtained. hK6-, hK8- and hK13-specific antibodies were produced and used for immunohistochemical analysis. Multiple KLK mRNAs were synthesized and used for in situ hybridization study. Three other hKs, namely hK6, hK8 and hK13, were immunohistochemically identified as new skin serine proteases in the whole SC, SG, sebaceous glands, eccrine sweat glands, hair follicles and nerves. We also demonstrated an increased number of cells expressing KLK mRNAs and hKs in PV and AD. In PV, KLK mRNAs/hKs were predominantly expressed in the upper epidermis. In AD, hK distribution was rather diffuse and expanded into the lower epidermis. The colocalization of various hKs seems to be essential for the regulation of serine protease activity in skin and for steady desquamation and skin barrier function. Moreover, the increased number of cells expressing multiple KLK mRNA and hK in PV and AD could be a clue to elucidate their pathogenesis.

The epidermal permeability barrier: from the early days at Harvard to emerging concepts.

The epidermal permeability barrier: from the early days at Harvard to emerging concepts.

Disorders of keratinization: diagnosis and management.

Disorders of cornification are a group of diseases that share abnormalities in the manufacture or desquamation of corneocytes. This paper reviews the major and a few of the rarer ones with a concentration on their therapy. Ichthyosis vulgaris is probably a post-translational defect in pro-filaggrin expression. It shows fine white flaky scales of the extensor surfaces, trunk, flank, lower legs but spares the folds and wet areas. Treatment is with aggressive moisturization. Hydrocortisone creams may be needed to control itch. Recessive X-linked ichthyosis is due to a deficiency of cholesterol sulfatase. Boys with this condition show small dark scales around the ears, sides of the neck, extensor surfaces of the arms and legs, and the peri-umbilical region. It spares the folds and face. Treatment is with moisturizers, topical retinoid creams or with topical cholesterol-based creams. Checking for signs of contiguous gene disorders (Kallman or Conradi-Hunermann syndromes) is necessary. Bullous congenital ichthyosiform erythroderma is caused by mutations in keratins 1 and/or 10. These patients are born as bright red babies with large blisters and erosions. Slowly, a porcupine quill-like waxy scaling develops. Blistering continues throughout life. Secondary infections of the skin cause pain, debility, and a very foul odor. Treatment is difficult. Topical moisturizers, descalers and retinoid creams help a little. Oral retinoids help a lot but can cause increased blistering. Controlling the odor is an ongoing issue using antibacterial washes, absorbing powders, and masking fragrances. Autosomal recessive ichthyosis is a term for both lamellar ichthyosis and congenital ishthysosiform erythroderma. They are caused by various mutations in transglutaminase-1 gene. In both instances patients are born as 'collodion babies'. Lamella ichthyosis has the very recognizable plate-like scale over the entire body. Children with congenital ishthysosiform erythroderma are red all over with a finer scale in some places and plate-like scales in others. Treatment is with topical moisturizers, retinoid creams, descalers, and in some cases oral retinoids. Palmar plantar keratodermas occur in conjunction with some ichthyoses, but also by themselves. Some are diffuse and others have discrete, corn-like hardenings. Treatment with topical acids, propylene glycol and retinoid creams help to some extent.Throughout the article pearls from my practice are included to assist the clinician in the day-to-day handling of these patients. A short section on genetic counseling concludes this article.

Expression and localization of tissue kallikrein mRNAs in human epidermis and appendages.

Tissue kallikreins are a group of serine proteases that are found in many organs and biologic fluids. Tissue kallikrein genes (KLKs) are found on chromosome 19q13.3-4 as a gene cluster encoding 15 different serine proteases. In skin, two tissue kallikrein proteins, hK5 and hK7, are expressed in the stratum corneum and are known to be involved in desquamation of corneocytes. The possible involvement of other kallikrein proteins has not been clarified, however, nor has the significance of each member in the serine protease activity of skin been delineated. In the study described here, we examined expression and localization of KLK mRNA in normal human skin by means of RT-PCR and in situ hybridization. Quantitative RT-PCR analysis showed abundant expression of KLK1 and KLK11 mRNA, moderate expression of KLK4, KLK5, KLK6, KLK7, and KLK13 mRNA, and low expression of KLK8 mRNA in normal human skin. For KLK4, KLK8, and KLK13 mRNA, splice variants were identified to be their major mRNA species. Two variants for KLK13 mRNA were novel. The amount of the serine protease inhibitor Kazal-type 5 (SPINK5) mRNA was comparable to KLK1 and KLK11 mRNA. In situ hybridization revealed intense expression of all KLK mRNA studied except KLK12 mRNA in the stratum granulosum of normal epidermis, where SPINK5 mRNA coexisted. Excluding KLK13 mRNA, they are also expressed in hair sheath, eccrine sweat glands, and sebaceous glands. Coexpression of various KLK and SPINK5 mRNA suggests that their proteins are the candidates to balance and maintain serine protease activities in both the skin and appendages.

Racial (ethnic) differences in skin properties: the objective data.

Racial (ethnic) differences in skin properties may explain racial disparities seen in dermatologic disorders and provide insight into appropriate differences in the management of these disorders. However, racial differences in skin have been minimally investigated by objective methods and the data are often contradictory. Objective methods studied include transepidermal water loss (TEWL), water content (WC), corneocyte variability, blood vessel reactivity, elastic recovery/extensibility, pH gradient, lipid content, surface microflora, microscopic evaluation of mast cell granules, and confocal microscopy. The majority of the evidence (six out of eight studies) indicates that TEWL is greater in Black skin compared with White skin. TEWL measurements of Asian skin are inconclusive as they have been found to be equal to Black skin and greater than Caucasian skin, equal to Caucasian skin, and less than all other ethnic groups in different studies. Racial differences in WC, as measured by resistance, capacitance, conductance and impedance, are also inconclusive as the data are contradictory. While the evidence regarding corneocyte desquamation is minimal, one clinically provocative observation is that Blacks have a 2.5 times greater spontaneous desquamation rate compared with Caucasians and Asians, possibly accounting for an increased frequency of xerosis seen clinically in Blacks. With regards to blood vessel reactivity, studies can not be compared to each other because each uses different vasoactive substances. However, each study, except for one study comparing Hispanics and Whites, and another comparing Japanese and German women, reveal some degree of racial variation in blood vessel reactivity. It has been demonstrated that the pH of Black skin is less than White skin; however, the studies that have demonstrated this have done so under different skin conditions and on different anatomic sites. Racial differences in lipid content are inconclusive. Additionally, there is insufficient and conflicting evidence to make conclusions regarding racial differences in skin biomechanics and skin microflora. Microscopic evaluation reveals that Black skin contains larger mast cell granules, and differences in stuctural properties and enzymes of mast cells compared with White skin, possibly accounting for differences in pruritus experienced by the individuals of these racial groups. There exists substantial evidence to support that Black skin has a higher TEWL, variable blood vessel reactivity, decreased skin surface pH, and larger mast cell granules compared with White skin. Although some deductions have been made about Asian and Hispanic skin, further evaluation needs to be done. Differences in WC, corneocyte desquamation, elastic recovery/extensibility, lipid content and skin microflora, although statistically significant, are inconclusive.

Elevated Stratum Corneum Hydrolytic Activity in Netherton Syndrome Suggests an Inhibitory Regulation of Desquamation by SPINK5-Derived Peptides

Netherton syndrome is a congenital ichthyosis associated with erythroderma, hair shaft defects, and atopic features. The mutations of the secretory serine protease inhibitor Kazal-type 5 gene have been identified in Netherton syndrome patients; however, the actual physiologic substrates of the serine protease inhibitor Kazal-type 5 proprotein are unknown, and how the genetic defects cause characteristic skin phenotype remains uncertain. Here, we describe the serine protease inhibitor Kazal-type 5 gene mutations, including two novel non-sense mutations, and genotype-phenotype correlation in three Netherton syndrome patients in two unrelated Japanese families. Furthermore, based on the reappraisal of the structure of the serine protease inhibitor Kazal-type 5 proprotein, demonstration of the presence of carboxypeptidase in normal keratinocytes, and the observation of mRNA localization of the serine protease inhibitor Kazal-type 5 transcripts in the uppermost epidermis as well as pilosebaceous units, we propose a hypothetical model of proteolytic processing of the serine protease inhibitor Kazal-type 5 proprotein in the epidermis and inhibitory regulation of corneocyte desquamation by a set of serine protease inhibitor Kazal-type 5-derived peptides. This hypothesis is supported by the marked increase of trypsin-like hydrolytic activity demonstrated in stratum corneum samples from our Netherton syndrome patients. The findings in this study suggest that the defective inhibitory regulation of desquamation due to the serine protease inhibitor Kazal-type 5 gene mutations may cause over-desquamation of corneocytes in Netherton syndrome, leading to severe skin permeability barrier dysfunction.

Dry Skin

Though there is ambiguity in its medical definition, dry skin is a frequent skin problem of increasing importance these days. Generally "dry skin" denotes the status of skin showing erythema, roughness, scales, and itching resulted from low water content in the skin. Abnormalities in epidermal lipids, natural moisturizing factors, or corneocyte desquamation are regarded as important factors in its pathophysiology. It is not only accompanied with skin aging, but with various kinds of skin and systemic diseases(such as atopic dermatitis, ichthyosis, chronic renal failure, and diabetes mellitus). Important principles in the management or treatment of dry skin are preventing excessive washing and keeping moisture in the epidermis. For gentle cleansing, mild surfactants are better than the soap. Moisturizers are applied to the surface of skin to increase epidermal water content. Two different kinds of moisturizers are used as a mixture for the best result. Humectants are the material that draw water from the air or dermis. And emollients are the material that protects membrane by preventing water from evaporating from the epidermis. Though moisturizers are very helpful in management of dry skin, harmful result may happen by inadequate selection and wrong use.

Corneocyte desquamation.

Corneocyte desquamation at the skin surface is a complex biologic event which is normally regulated for providing an inconspicuous shedding of single corneocytes. When altered, the process gives rise to xerotic and ichthyotic conditions. The present review focusses on important biologic and molecular aspects responsible for normal and altered corneocyte desquamation. There is a complex relationship between epidermal cell production, maturation and desquamative loss. Corneocyte hydration, stratum corneum barrier function and enzymatic corneodesmolysis are involved in a dynamic interrelationship. Many physiological and environmental factors acting in a different time frame influence desquamation.

Stratum corneum, corneodesmosomes and ex vivo percutaneous penetration.

The stratum corneum is composed of cornified keratinocytes, joined together with corneodesmosomes and embedded in the relatively hydrophobic intercellular substance. Formation of this horny layer and its constant desquamation are fundamental processes leading to the establishment of an efficient epidermal barrier. We examined structural changes occurring in the stratum corneum ex vivo, in order to better understand the mechanisms regulating corneocyte desquamation at the epidermal surface and influencing percutaneous penetration of exogenous substances. Morphologic modifications were induced by occlusion, increasing the tissue hydration, or by application of propylene glycol, a hydrophilic solvent of small molecular size. Distribution of the major epidermal antigens, markers of terminal differentiation, was studied immunohistochemically and showed no modification related to the tissue alteration. Skin samples were fixed in paraformaldehyde and either postfixed in OsO4 and embedded in Epon or postfixed in RuO4 and embedded in epoxy and acrylic resins. Structural composition and spatial organization of the elements present in the intercorneocyte spaces were evaluated ultrastructurally, with special attention paid to the fate of corneodesmosomes. Our results suggest that the spontaneous organization of lipids excreted into the intercellular spaces and constitution of the lamellar multilayers in the lower stratum corneum are at the origin of partition of the intercellular compartment to the hydrophobic and hydrophilic domains. The latter, compatible with the proteinic contents, seem to be displaced by the hydrophobic components undergoing reorganization, towards the invariable hydrophilic foci represented by corneodesmosomes. This mechanism may be involved in the delivery of proteolytic enzymes, thus contributing to the progressive degradation of corneodesmosomal proteins.

The pH Gradient over the Stratum Corneum Differs in X-Linked Recessive and Autosomal Dominant Ichthyosis: A Clue to the Molecular Origin of the “Acid Skin Mantle”?

In a search for pathogenetic mechanisms underlying retention hyperkeratosis, we examined the pH gradient over the stratum corneum in 13 male patients suffering from either x-linked recessive (XRI) or autosomal dominant ichthyosis vulgaris. For recording pH values, a flat glass electrode was repeatedly applied to the skin during tape stripping of mildly involved forearm skin. Before stripping, surface pH was higher in ichthyosis vulgaris (5.3 +/- 0.7; n = 7) than in XRI (4.6 +/- 0.4; n = 6; p < 0.05) and healthy control men (4.5 +/- 0.2; n = 7; p < 0.01). Removal of stratum corneum, which required 100-240 strippings in ichthyotic skin and 80-120 strippings in healthy control skin, disclosed markedly different pH variations in the two types of ichthyosis. The major abnormality in ichthyosis vulgaris skin was that a neutral pH was attained already halfway through the horny layer, possibly reflecting a congenital lack of acidic breakdown products from keratohyaline. By contrast, stripping of XRI skin revealed a shallow pH gradient that plateaued at 6.2-6.6, instead of about 7 as in normal and ichthyosis vulgaris skin. A likely explanation is the XRI-associated accumulation of cholesterol sulfate in lower stratum corneum. Our results suggest that the "acid mantle" of normal skin, which penetrates deep into the stratum corneum, is the combined result of cornification-associated organic acids and back-diffusion of acid material from the surface. Because corneocyte desquamation involves many pH-dependent enzymes, abnormalities in the transcorneal pH gradient might play a role in the pathogenesis of ichthyosis.

The Structure and Function of Epidermal Lipids

Abstract— This review article examines current knowledge of the structure and function of epidermal lipids in human and veterinary dermatology. Dynamic transformations in lipid composition and structure occur as cells migrate through the epidermis. The lipids which are formed have a direct effect on epidermal functions. Ceramides appear to be the most important lipid component for lamellar arrangement in the stratum corneum and barrier protection. Polyunsaturated fatty acids in the epidermis are also important because they are incorporated into the ceramides. Additionally, arachidonic acid is bound to the phospholipid portion of cell membranes and is the most important precursor of endogenous eicosanoids. The eicosanoids are vital for epidermal homeostasis and play an important role in the pathogenesis of inflammatory dermatoses when produced in abnormal quantities. In addition to barrier protection, other vital epidermal functions associated with the lipids include stratum corneum water‐holding, cohesion and desquamation of corneocytes, and control of epidermal proliferation and differentiation.

Composition of cerumen lipids

Lipids were extracted from "wet" cerumen and analyzed by quantitative thin-layer chromatography to determine their composition. The lipid fraction comprised 52% of the dry weight of cerumen and consisted of squalene (6.4%), cholesterol esters (9.6%), wax esters (9.3%), triacylglycerols (3.0%), fatty acids (22.7%), cholesterol (20.9%), ceramides (18.6%), cholesterol sulfate (2.0%), and several unidentified polar components (7.5%). In addition to the extractable lipids, the residue contained an additional 0.9% lipid that could be released only after saponification. This covalently bound lipid consisted of two unusual ceramides (63.4%), omega-hydroxyacids (27.7%) and nonhydroxy fatty acids (8.8%). The composition of this bound lipid resembled that recently found in human stratum corneum, which is thought to comprise a lipid envelope on the outer surface of the corneocytes. The free and covalently bound lipids may be significant determinants of the properties of cerumen. Desquamation of corneocytes and their associated lipids from the epidermal lining of the ear canal may make a major contribution to cerumen.