Plantar Epidermis Research Articles

Inhibiting EGFR Signaling Holds Promise for Treating Palmoplantar Keratodermas

PC is a rare condition (∼10 thousand cases worldwide) featuring anomalies that affect ectoderm-derived appendages, including nail dystrophy, sebaceous cysts, natal teeth, oral leukokeratosis, and PPK (Leachman et al., 2005). PPK consists of extreme thickening of the skin of palms and especially soles and develops primarily in areas of skin experiencing high pressure or compression stress. Histologically, there is a dramatic thickening of the living and stratum corneum compartments, known as acanthosis and hyperkeratosis, respectively, in the palmar and especially the plantar epidermis in PC (Cao et al., 2015).

PRIMARY PREVENTION OF VERRUCA PLANTARIS THROUGH TOPICAL HERBAL AND VITAMIN DERIVATIVE

Objective: Verrucae plantaris (VP) results from environmental exposure to human papillomavirus causing plantar warts of the foot, resistantto treatment, and high recurrence rates. Current treatment paradigms focus on the treatment of lesions as opposed to primary prophylaxis. Wehypothesize that a topical combination of herbal supplement with anti-viral properties and a vitamin derivative* can be used prophylactically todecrease the primary incidence.Methods: We initiated a double-blinded clinical study with participants (n=282) randomization into control (lotion emollient only) (n=120),treatment (herbal and vitamin derivative) (n=110) and no treatment (NT) (n=52). Participants underwent examination of the feet at baseline (0months) to exclude VP lesions and were randomized to receive a bottle containing topical lotion with emollient only, control (C), lotion with an herbaland vitamin derivative, treatment (T), or NT, where participants did not apply anything to their feet. C and T participants applied lotion topically to thefeet once daily and were examined at 3, 6, 9, and 12 months to document the incidence of VP.Results: No incidence of VP occurred in the T group (0/110=0% incidence), two lesions in the C group (2/120=1.7% incidence), and five lesions inthe NT group (5/52=9.6% incidence).Conclusion: Treatments for VP rely on treating lesions after they occur, have high degrees of variability in success, risk of continued transmissionduring treatment, and have high rates of recurrence. Although the study number is relatively low, early indications show decreasing incidence ofVP from 9.6% in participants with NT to 1.7% in participants who used lotion only, suggesting increased health of the plantar epidermis, and 0%incidence in those participants applying topical herbal and vitamin derivative*. Additional study with increased numbers of participants is warranted.

Keratins K2 and K10 are essential for the epidermal integrity of plantar skin

BackgroundK1 and K2 are the main type II keratins in the suprabasal epidermis where each of them heterodimerizes with the type I keratin K10 to form intermediate filaments. In regions of the ears, tail, and soles of the mouse, only K2 is co-expressed with K10, suggesting that these keratins suffice to form a mechanically resilient cytoskeleton. ObjectiveTo determine the effects of the suppression of both main keratins, K2 and K10, in the suprabasal plantar epidermis of the mouse. MethodsKrt2−/− Krt10−/− mice were generated by crossing Krt2−/− and Krt10−/− mice. Epidermal morphology of soles of hind-paws was examined macroscopically and histologically. Immunofluorescence analysis and quantitative PCR analysis were performed to analyze the expression of keratins in sole skin of wildtype and Krt2−/− Krt10−/− mice. Highly abundant proteins of the sole stratum corneum were determined by electrophoretic and chromatographic separation and subsequent mass spectrometry. ResultsK2 and K10 are the most prominent suprabasal keratins in normal mouse soles with the exception of the footpads where K1, K9 and K10 predominate. Mice lacking both K2 and K10 were viable and developed epidermal acanthosis and hyperkeratosis in inter-footpad epidermis of the soles. The expression of keratins K1, K9 and K16 was massively increased at the RNA and protein levels in the soles of Krt2−/− Krt10−/− mice. ConclusionsThis study demonstrates that the loss of the main cytoskeletal components of plantar epidermis, i.e. K2 and K10, can be only partly compensated by the upregulation of other keratins. The thickening of the epidermis in the soles of Krt2−/− Krt10−/− mice may serve as a model for pathomechanistic aspects of palmoplantar keratoderma.

Pitted keratolysis: a clinical review.

Pitted keratolysis is a bacterial infection that affects the plantar epidermis. Despite the condition being reported in many countries affecting both shod and unshod populations, there is little guidance for clinicians providing evidence or best practice guidelines on the management of this often stubborn infection. Using a structured search of a range of databases, papers were identified that reported treatments tested on patients with the condition. Most of the literature uncovered was generally of a low level, such as case-based reporting or small case series. Studies were focused mainly on the use of topical antibiotic agents, such as clindamycin, erythromycin, fusidic acid, and mupirocin, often in combination with other measures, such as hygiene advice and the use of antiperspirants. From the limited evidence available, the use of topical antibiotic agents shows some efficacy in the treatment of pitted keratolysis. However, there is currently no suggestion that oral antibiotic drug therapy alone is effective in managing the condition. Currently, there is no consensus on the most effective approach to managing pitted keratolysis, but a combination of antimicrobial agents and adjunctive measures, such as antiperspirants, seems to demonstrate the most effective approach from the current literature available.

Relationship between the Three-Dimensional Structure of the Human Plantar Epidermis and the Dermoscopic Patterns Seen in Melanocytic Nevi

Objective: Our aim was to investigate the relationship between the distribution of the dermoscopic patterns seen in plantar melanocytic nevi and the 3-dimensional structures of the epidermis. Methods: The precise locations of 69 melanocytic nevi on the sole and the border areas were investigated, with attention paid to each dermoscopic pattern. In addition, the basal surfaces of the plantar epidermis from 14 anatomical areas were observed by scanning electron microscopy (SEM). Results: In the weight-bearing area, melanocytic nevi with a fibrillar pattern were preferentially observed. Those with a lattice-like pattern were observed in the arch area, whereas those with a crista reticulated pattern were seen in the border area. On SEM observations, transverse ridges formed a couple of parallel lamellae on the crista profunda limitans (limiting ridges). Between the limiting ridges and the crista profunda intermedia (intermediate ridges), the transverse ridges had different shapes according to the anatomical location of the sole. Conclusion: These results suggest that the characteristic dermoscopic patterns seen in plantar melanocytic nevi simulate the arrangement of transverse ridges.

Correspondence between dermoscopic features and epidermal structures revealed by scanning electron microscope

It is already known that some typical dermoscopic patterns seen in melanocytic nevi on the sole have their own favorite site. In the weight-bearing area, melanocytic nevi with a parallel furrow pattern were preferentially observed. Those with a lattice-like pattern were observed in the arch area, whereas those with a crista reticulated pattern were seen in the border area. To investigate the relationship between the distribution of the dermoscopic patterns seen in plantar melanocytic nevi and the 3-D structures of the epidermis, the basal surfaces of the plantar epidermis from 14 skin lesions were observed by scanning electron microscopy (SEM). Our SEM observations revealed that transverse ridges formed a couple of parallel lamellae on the crista profunda limitans (limiting ridges). Between the limiting ridges and the crista profunda intermedia (intermediate ridges), the transverse ridges had different shapes according to the anatomical location of the sole. From these results, it was suggested that the characteristic dermoscopic patterns seen in acquired and junctional melanocytic nevi on the sole simulate the arrangement of transverse ridges.

Diagnosing SAPHO Syndrome in Suspected Metastatic Bone Tumors

Abstract: A previously healthy 44-year-old woman who had been followed at different health care facilities for symptoms which had begun 3 years earlier was referred to our service for clinical evaluation. Her problems during the initial examination were pain in the sternoclavicular and sacroiliac joints as well as plantar pustulitis. Based on previous x-ray hyperostosis findings, metastatic bone tumors to the spine and first costocondral junctions bilaterally were suspected. A biopsy of the sternoclavicular lesion showed a nonspecific inflammation pattern. On the first physical examination we found a nontender swelling of the sternoclavicular junctions, necrosis of the plantar epidermis and pain at the sacroiliac joints. The patient was referred for bone scintigraphy and positron emission tomography-computed tomography (PET-CT) scan. The whole body bone scintigraphy using Tc-99m MDP showed increased accumulation of the radiotracer in the anterior chest wall and in the right sacroiliac joint. Metastatic bone tumor was not suggested, although exclusion of bone metastases was difficult. The PET-CT with F-18 FDG showed areas with low metabolic activity in the anterior chest wall (SUV Max: 1.96) and in the right sacroiliac joint (SUV Max: 2.18) making the diagnosis of malignancy and acute infection unlikely. The clinical symptoms, the typical skin lesions involving the soles of the feet and low hypermetabolic lesions on PET-CT made the final diagnosis of SAPHO syndrome.

Keratin K6c Mutations Cause Focal Palmoplantar Keratoderma

The palmoplantar keratodermas (PPKs) are a large group of clinically and genetically heterogeneous genodermatoses. The gene defects underlying many PPKs still need to be resolved to facilitate definitive molecular diagnosis and genetic counseling. Dominant-negative mutations in any of the four identified keratin genes, KRT6A, KRT6B, KRT16, or KRT17, cause pachyonychia congenita (PC), characterized by hypertrophic nail dystrophy and other ectodermal features. In PC, focal PPK (FPPK) is the most painful and debilitating phenotypic feature. Some families presenting with FPPK alone, or with minimal nail changes, carry mutations in KRT16; however, most FPPK families do not harbor mutations in any of these keratin genes. Here, we report three unrelated families who presented with familial FPPK with minor or absent nail changes. The four PC/FPPK-related keratin genes were excluded; however, mutational analysis of the recently identified KRT6C gene, encoding keratin K6c, showed heterozygous in-frame deletion mutations in all three kindreds. Affected members of Families 1 and 2 carried the same mutation, p.Asn172del. In Family 3, the mutation p.Ile462-Glu470del co-segregated with the disease. KRT6C was shown to be expressed in the plantar epidermis using reverse transcription-PCR, consistent with the phenotype observed in this tissue. These data expand the genetic testing repertoire for the PPKs.

Scale architecture of the palmar and plantar epidermis of Polychrus acutirostris Spix, 1825 (Iguania, Polychrotidae) and its relationship to arboreal locomotion

In tetrapod squamates, the diversity of micro-ornamentations of the epidermis of the contact areas of hands and feet is generally associated with constraints and modalities related to locomotion. Polychrus acutirostris is a medium-sized lizard that occurs in open heterogeneous habitats in South America, such as the cerrados, caatingas, and fallow lands. It progresses slowly on branches of various diameters in its arboreal environment. It can also move more rapidly on the ground. The hands and feet are prehensile and may be considered an adaptation for grasping and climbing. Epidermal surfaces from the palmar and plantar areas of the hands and feet of P. acutirostris were prepared for SEM examination, and studied at various magnifications. They show three major levels of complexity: (1) scale types, organized in gradients of size and imbrication, (2) scalar ornamentations, organized by increasing complexity and polarity, and (3) presence of Oberhäutchen showing typically iguanian honeycomb micro-ornamentations. The shape and surface structure of the scales with their pattern of micro-ornamental peaks, which improve grip, and the grasping hands and feet indicate that P. acutirostris is morpho-functionally specialized for arboreality.

Peripheral administration of CRH antagonist improves gastrointestinal motility, visceral perception, and negative moods in response to gut stimulation in BS patients

Differentiation of human plantar and palmar epidermis is characterized by the suprabasal synthesis of a major special intermediate-sized filament (IF) protein, the type I (acidic) cytokeratin 9 (CK 9). Using partial amino acid (aa) sequence information obtained by direct Edman sequencing of peptides resulting from proteolytic digestion of purified CK 9, we synthesized several redundant primers by ‘back-translation’. Amplification by polymerase chain reaction (PCR) of cDNAs obtained by reverse transcription of mRNAs from human foot sole epidermis, including 5′-primer extension, resulted in multiple overlapping cDNA clones, from which the complete cDNA (2353 bp) could be constructed. This cDNA encoded the CK 9 polypeptide with a calculated molecular weight of 61987 and an isoelectric point at about pH 5.0. The aa sequence deduced from cDNA was verified in several parts by comparison with the peptide sequences and showed the typical structure of type I CKs, with a head (153 aa), an a-helical coiled-coil-forming rod (306 aa), and a tail (163 aa) domain. The protein displayed the highest homology to human CK 10, not only in the highly conserved rod domain but also in large parts of the head and the tail domains. On the other hand, the aa sequence revealed some remarkable differences from CK 10 and other CKs, even in the most conserved segments of the rod domain. The nuclease digestion pattern seen on Southern blot analysis of human genomic DNA indicated the existence of a unique CK 9 gene.Using CK 9-specific riboprobes for hybridization on Northern blots of RNAs from various epithelia, a mRNA of about 2.4 kb in length could be identified only in foot sole epidermis, and a weaker cross-hybridization signal was seen in RNA from bovine heel pad epidermis at about 2.0 kb. A large number of tissues and cell cultures were examined by PCR of mRNA-derived cDNAs, using CK 9-specific primers. But even with this very sensitive signal amplification, only palmar/ plantar epidermis was found positive. By in situ hybridization and immunolocalization we further showed that CK 9 is only expressed in the suprabasal cell layers of this special epidermal tissue. We discuss the molecular properties of CK 9 and its cell type- and body site-specific expression in relation to the special differentiation of palmar/plantar epidermis and to diseases specific for this body site.

Covering the limb--formation of the integument.

An organism's outermost covering, the integument, has evolved to fulfil a diverse range of functions. Skin provides a physical barrier, an environment for immunological surveillance, and also performs a range of sensory, thermoregulatory and biosynthetic functions. Examination of the skin of limb digits reveals a range of skin types including the thickened hairless epidermis of the toe pads (palmar or plantar epidermis) and thinner epidermis between the hair follicles (interfollicular epidermis) of hairy skin. An important developmental function of skin is to give rise to a diverse group of appendages including hair follicles, with associated sebaceous glands (or feathers and scales in chick), eccrine sweat glands and the nail. A key question is how does this morphological variety arise from the single-layered epithelium covering embryonic limb buds? This review will attempt to address this question by linking the extensive morphological/anatomical data on maturation of epidermis and its appendages with (1) current research into the range, plasticity and location of the putative epidermal stems cells; (2) molecular/microenvironmental regulation of epidermal stem cell lineages and lineage choice; and (3) regulation of the differentiation pathways, focusing on differentiation of the interfollicular epidermis.

Upregulation of Connexin 26 is a Feature of Keratinocyte Differentiation in Hyperproliferative Epidermis, Vaginal Epithelium, and Buccal Epithelium

In epidermis, it has been suggested, intercellular communication through gap junctions is important in coordinating cell behavior. The connexins, may facilitate selective assembly or permeability of gap junctions, influencing the distribution of metabolites between cells. Using immunohistochemistry, we have compared the distribution of connexins 26 and 43 with that of proliferating cells (Ki67 labeling) in normal epidermis, hyperplastic epidermis (tape-stripped epidermis, psoriatic lesions, and viral warts), and vaginal and buccal epithelia. Connexin 43 was abundant in spinous layers of all epidermal specimens and in vaginal and buccal epithelia. Connexin 26 was absent from the interfollicular and interductal epidermis of normal hair-bearing skin, and nonlesional psoriatic epidermis but present at very low levels in plantar epidermis. Connexin 26 was prominent in lesional psoriatic epidermis and viral warts and in vaginal and buccal epithelia. In three independent experiments connexin 26 appeared in a patchy intercellular distribution in the basal epidermis within 24 h of tape stripping, proceeding to more extensive distribution in basal and suprabasal layers by 48 h. The increase in connexin 26 preceded that in cell proliferation. In vaginal epithelium, buccal epithelium, and viral warts connexin 26 was restricted mainly to suprabasal, nonproliferating cells. In psoriatic lesional epidermis connexin 26 was also located mainly in suprabasal, nonproliferating cells. Connexin 26 was present in a patchy distribution in the basal layer of psoriatic lesional epidermis, but double labeling for connexin 26 and Ki67 showed that many connexin 26 positive basal cells were nonproliferative, suggesting that connexin 26 may be related to differentiation rather than to proliferation. These observations would be consistent with a role for connexin 26 containing gap junctions during both early and later stages of keratinocyte differentiation in hyperplastic epidermis and in vaginal and buccal epithelia.

Evidence that filaggrin is a component of cornified cell envelopes in human plantar epidermis

Cornified cell envelope (CE) is generated during the late stages of epidermal differentiation and is made up of proteins covalently linked together by transglutaminases. To determine whether filaggrin is a component of this structure in humans, we analysed highly purified CE from plantar stratum corneum. An immunoelectron microscopy analysis showed specific binding of four different anti-(pro)filaggrin monoclonal antibodies to the surface of the CE, proved previously to be free of non-covalently linked proteins. Moreover, the anti-filaggrin activity of one of the antibodies was absorbed by preincubation with the plantar CE, as determined by ELISA. Convincingly, fragments of CE produced by proteolytic digestion of the structures were stained by this antibody on immunoblots. These data provide direct evidence that filaggrin is a component of CE purified from human plantar stratum corneum. Cross-linking between CE and the filaggrin-containing fibrous matrix may enhance the structural cohesion of the corneocytes and thus the resistance of the stratum corneum.

A novel monoclonal antibody to the outer root sheath cells

A novel monoclonal antibody to hair keratins (TYHF-1) which recognized a doublet of 43 44 - kDa hair keratins in the immunoblot analysis was developed. TYHF-1 strongly reacted with the outer root sheath cells at the region of prekeratinization, the keratogeneous zone and the lower part of the isthmus portion in the indirect immunofluorescent examination. The cells of the inner root sheath and cuticle in the upper bulbar portion were also stained with this antibody. In addition, the tongue and nail matrix were also reacted with TYHF-1. However, TYHF-1 reacted with no epidermal keratins either in the indirect immunofluorescent examination or by immunoblot analysis using plantar epidermis. In addition, the cells of the eccrine and apocrine sweat glands, the epithelia of the buccal mucosa, larynx, tonsil, oesophagus, liver, intestine, gallbladder and urinary bladder demonstrated no positive reaction.

Molecular characterization of the body site-specific human epidermal cytokeratin 9: cDNA cloning, amino acid sequence, and tissue specificity of gene expression

Abstract Differentiation of human plantar and palmar epidermis is characterized by the suprabasal synthesis of a major special intermediate-sized filament (IF) protein, the type I (acidic) cytokeratin 9 (CK 9). Using partial amino acid (aa) sequence information obtained by direct Edman sequencing of peptides resulting from proteolytic digestion of purified CK 9, we synthesized several redundant primers by ‘back-translation’. Amplification by polymerase chain reaction (PCR) of cDNAs obtained by reverse transcription of mRNAs from human foot sole epidermis, including 5′-primer extension, resulted in multiple overlapping cDNA clones, from which the complete cDNA (2353 bp) could be constructed. This cDNA encoded the CK 9 polypeptide with a calculated molecular weight of 61987 and an isoelectric point at about pH 5.0. The aa sequence deduced from cDNA was verified in several parts by comparison with the peptide sequences and showed the typical structure of type I CKs, with a head (153 aa), an a-helical coiled-coil-forming rod (306 aa), and a tail (163 aa) domain. The protein displayed the highest homology to human CK 10, not only in the highly conserved rod domain but also in large parts of the head and the tail domains. On the other hand, the aa sequence revealed some remarkable differences from CK 10 and other CKs, even in the most conserved segments of the rod domain. The nuclease digestion pattern seen on Southern blot analysis of human genomic DNA indicated the existence of a unique CK 9 gene. Using CK 9-specific riboprobes for hybridization on Northern blots of RNAs from various epithelia, a mRNA of about 2.4 kb in length could be identified only in foot sole epidermis, and a weaker cross-hybridization signal was seen in RNA from bovine heel pad epidermis at about 2.0 kb. A large number of tissues and cell cultures were examined by PCR of mRNA-derived cDNAs, using CK 9-specific primers. But even with this very sensitive signal amplification, only palmar/ plantar epidermis was found positive. By in situ hybridization and immunolocalization we further showed that CK 9 is only expressed in the suprabasal cell layers of this special epidermal tissue. We discuss the molecular properties of CK 9 and its cell type- and body site-specific expression in relation to the special differentiation of palmar/plantar epidermis and to diseases specific for this body site.

The basement membranes of cryofixed or aldehyde-fixed, freeze-substituted tissues are composed of a lamina densa and do not contain a lamina lucida

When tissues are processed for electron microscopy by conventional methods, such as glutaraldehyde fixation followed by rapid dehydration in acetone, basement membranes show two main layers: the electron-lucent "lamina lucida". (or rara) and the electron-dense "lamina densa". In an attempt to determine whether this subdivision is real or artefactual, two approaches have been used. Firstly, rat and mouse seminiferous tubules, mouse epididymis and associated tissues, and anterior parts of mouse eyes were subjected to cryofixation by instant freezing followed by freeze substitution in a -80 degrees C solution of osmium tetroxide in dry acetone, which was gradually warmed to room temperature over a 3-day period. The results indicate that, in areas devoid of ice crystals, basement membranes consist of a lamina densa in direct contact with the plasmalemma of the associated cells without an intervening lamina lucida. Secondly, a series of tissues from mice perfused with 3% glutaraldehyde were cryoprotected in 30% glycerol, frozen in Freon 22 and subjected to a 3-day freeze substitution in osmium tetroxide-acetone as above. Under these conditions, no lamina lucida accompanies the lamina densa in the basement membranes of the majority of tissues, including kidney, thyroid gland, smooth and skeletal muscle, ciliary body, seminiferous tubules, epididymis and capillary endothelium. Thus, even though these tissues have been fixed in glutaraldehyde, no lamina lucida appears when they are slowly dehydrated by freeze substitution. It is concluded that the occurrence of this lamina in conventionally processed tissues is not due to fixation but to the rapid dehydration. However, in this series of experiments, the basement membranes of trachea and plantar epidermis include a lamina lucida along their entire length, while those of esophagus and vas deferens may or may not include a lamina lucida. To find out if the lamina lucida appearing under these conditions is a real structure or an artefact, the trachea and epidermis were fixed in paraformaldehyde and slowly dehydrated by freeze substitution. Under these conditions, no lamina lucida was found. Since this result is the same as observed in other tissues by the previous approaches, it is proposed that the lamina lucida is an artefact in these as in the other investigated basement membranes. Thus, basement membranes are simply composed of a lamina densa that closely follows the plasmalemma of the associated cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Composition of Free Long-Chain (Sphingoid) Bases in Stratum Corneum of Normal and Pathologic Human Skin Conditions

The composition of molecular species of free long-chain bases (FLCB) isolated from stratum corneum of various human skin conditions was analyzed by the high-performance liquid chromatographic and fast atom bombardment mass spectrometric methods. FLCB with carbon length ranging from 16 to 20 comprised about 0.3% of total lipids in stratum corneum of normal and pathologic skin conditions. Major FLCB included sphinganines and sphingenines with 18 to 20 carbons and some phytosphingosines such as t17:1, t18:1, t18:0, t20:1, and t20:0. Compared with stratum corneum of normal lower legs, molar percentages of FLCB having 18 carbons and those with 20 carbons were slightly higher and lower, respectively, in normal plantar epidermis, showing site-related differences in normal skin. Psoriatic scales and hyperkeratotic stratum corneum from clavus and plantar keratoderma contained increased levels of FLCB with 18 carbons and decreased levels of FLCB with 20 carbons. These findings may reflect abnormal keratinization in hyperkeratotic skin conditions.

The expression of desmosomal and corneodesmosomal antigens shows specific variations during the terminal differentiation of epidermis and hair follicle epithelia.

Using five monoclonal antibodies (MAb), we studied by indirect immunofluorescence the desmosomes and a junctional structure specific to cornified layers, the corneodesmosome, in normal and plantar epidermis and in the various sheaths of the anagen hair follicle. The monoclonal antibodies DP1&2.2-15, PG5.1, and DG3.10, specific for desmoplakins I/II, plakoglobin, and desmoglein I, respectively, were used to study the desmosome antigens, and G36-19 and G20-21 to study the corneodesmosome antigens. The distribution and sequence of expression of the five antigens allowed the nine epithelial differentiation pathways studied to be merged into four distinct families: non-plantar epidermis, characterized by the absence of desmosome and corneodesmosome antigens in the stratum corneum; the outer root sheath of the hair follicle, which behaves like the viable layers of the epidermis with regard to the desmosome antigens but does not express the corneodesmosome antigens; plantar epidermis and the three components of the inner root sheath in which the corneodesmosome antigens are present up to the desquamating layer; and the three components of the hair shaft, which are characterized by the absence of expression of both the desmosome and the corneodesmosome antigens in its mature portion.

2D-page and amino acid analysis of the keratins extracted from the plantar epidermis of a tyrosinemia type II patient

2D-page and amino acid analysis of the keratins extracted from the plantar epidermis of a tyrosinemia type II patient

Bicomponent keratohyalin in normal human ridged skin

Up to now, bicomponent keratohyalin has only been described for rat epithelium and human intraepidermal sweat ducts and fetal nail organ cells. In normal human interductal epidermis, the keratohyalin appears homogeneous, osmiophilic and stellate in shape. Under pathological conditions, bicomponent keratohyalin has been observed in different palmoplantar keratoses and has therefore been thought to be associated with abnormal keratosis. We studied the keratinization process in normal human plantar epidermis, in which keratohyalin was found to exhibit several morphological differences as compared to that seen in non-ridged skin. The most striking feature was seen in upper granular cells, where the keratohyalin granules consisted of two components of differing electron density. The electron-dense component formed the main part of the composite granule and was found in the cytoplasm of lower and upper granular cells. The less-electron-dense component was attached to the main component and appeared in the cytoplasm of upper granular cells, forming the convex contact zone. No intranuclear osmiophilic inclusions were present. The respective electron densities of the two keratohyalin components of ridged skin were obviously different to that of the bicomponent keratohyalin granules seen in the epidermal sweat-duct cells of the same specimen. These findings indicate the presence of at least two different types of keratohyalin proteins in normal human ridged skin. They can be distinguished at the electron-microscope level and differ from the keratohyalin of human non-ridged skin as well as from bicomponent keratohyalin granules derived from human epidermal sweat-duct cells or from rat epithelium.