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Biochemical Composition of the Epidermal-Dermal Junction and Other Basement Membrane

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Biochemical Composition of the Epidermal-Dermal Junction and Other Basement Membrane 0022-202X/ 82/780 J -000 I $02.00/ 0 TH E J OUHNAL OF I NVESTI GATIVE 0EHMAT OL0GY, 78: 1-6. 1982 Vol. 78, No. I Copyright © 1982 by The Williams & Wil ki ns Co. Pri11t ed i11 U.S.A . Reprinted from REVIEW ARTICLE Progress in Dermatology a bulletin published by t he DERM ATOLOGY FOUNDATION Co- Edi tors: Robert A. Brigga man, M.D. Lowell A. Goldsmith, M .D. North Carolina Memori al H ospita l Box :.l0:10, Duke Medical Center Chapel Hill , Nort h Caroli na ~75 1 5 Du rham, North Carolina 277 10 Biochemical Composition of the Epidermal-dermal Junction and Other Basement Membrane R oBE RT A. B RIGGAMAN, M.D. Professor of Dermatology, University of North Ca.rolina, School of Medicine, Department of Dermatology, Chapel Hill, North Carolina. U.S.A. During t he last several yeaTs, our knowledge of the biochem­ of the internal leaflet of the p lasma membrane. To no filaments ical composition of the e pidermal-dermal junction and the course toward the attachment plaque but actually terminate in ultrastructural location of the pathologic reaction in numerous a relatively electron dense zone separated from the plaque by skin diseases that affect this area has increased greatly. In this a narrow electron lu cent zone. paper, our purpose is to review current information in these T he lamina lucida (intermembraneous space, lamina rara) is areas. The epidermal-dermal junction h as been reviewed pre­ an electron lucent ru·ea located between the plasma membrane viously a nd the reader i s referred to these som ces for a more of the basal keratinocyte and the underlying basal lamina. general a nd comprehensive review of the subject [1-5). Lamina lucida is approximately 20-40 nm in thickness and is First, a brief review of the ultrastructural m orphology of the amorphous in most areas. In the lamina Iucida subjacent to epidermal-dermal junction is necessary to relate the subsequent hemidesmosomes a special structme termed the sub-basal studies. The e pidermal-dermal junction i s more complex and dense plaque appears as an electron dense line beneath the more highly organized ultrastructurally t han the s imple linear hemidesmosome. In this area, fine filaments traverse the lamina "basem ent membrane zo ne" between epidermis a nd dermis Iucida perpendicularly a nd mesh with the basal lamina. These noted b y light microscopy. Three different epidermal cell types, filaments have been called anchoring filaments. basal keratinocyte, melanocyte, and Merkel cell, c omprise a T he basal l amina (lamina densa) is a continuous electron portion of the e pidermal-dermal junction wi th each cell type dense layer which runs pru·allel to the plasma membrane, presenting a somewhat diffe rent a ppearance at the junction. sepru·ated from i t by the lamina Iucida. T he basal l amina has B asal keratinocytes form the vast majori ty of the junction zone an am orphous fine granulru· appearance and, although some­ and will be t he only cell considered h ere. The epidermal-dermal what vru·iable in thickness and density, measw-es approximately junction b etween b asal keratinocytes and dermis can be di ­ 30-50 nm. Reduplication of the basal lamina is relatively com­ vided, for convenience, into 4 ru·eas proceeding from epidermis mon even in normal skin and may result from remodeling of toward the dermis (Figure). These ru·e: The basal cell plasma the epidermal-dermal junction as a fu nction of cell detachment, membrane wit h its special attachment structures, hemidesmo­ migration, and re-attachment in this area. Reduplication of the somes; lamina Iucida; th e basal lamina; and a sub-basal lamina basal lamina a nd other junctional structm es may be markedly fibrous zone. exaggerated in a variety of pathologic processes that affect the The plasma membrane of basal keratinocytes is a t rilaminar junctional zone. Mru·ked reduplication of basal lrunina is the structure measuring a pproximately 7-9 nanometers (nm) in ultrastructural counterpru·t of the basement membrane thick­ thickness. Electron d ense thickenings stud the p lasma mem­ ening, for example, as noted in cutaneous lupus erythematosus. brane a t frequent intervals. These structures are termed h emi­ The subbasal lamina fibrous ru·ea is situated immediately desmosomes and are diagramatically presented in the Figm e. beneath the basal lamina a nd is composed of three different T he hemidesmosome is composed of an electron d ense area, types of fibrous structures: anchoring fibrils, der mal microfibril the a ttachment plaque, that is present o n the cytoplasmic side bundles, and collagen fi bers. Anchoring fibrils have a unique structm·e which consist of a central, asymmetrically cross­ banded r egion with fa n-like ru-rays of smaller fibrillar compo­ This work was supported b y Research Grant 2 HOl AM 1054G, National Institutes of Health. nents extending from both ends. T he epidermal end of the Reprint requ ests to: Dr. Roberl A. Brigga man, Department of Der­ anchoring fibril meshes with the basal lamina while the dermal matology, The Un iversity of N orth Caro lina, School of M edi cine, end extends into the dennis. Frequently, the dermal portions of Chapel Hill, NC 27514. adjacent a nchoring fibrils fuse forming a n interlocki ng mesh- 2 BRIGGAMAN Vol. 78, No. 1 work in the d~rmis below the basal lamina. Collagen fibers are distinctive component in the sub-basal lamina area. These sometimes caught up in this mesh-work or surrounded by loops consist of bundles of parallel fibrils which pass deep into the of connecting anchoring fibrils but are never directly connected dermis essentially perpendicularly from the epidermal-dermal to the anchoring fibril. The dermal microfibril bundle is a junction. The epidermal ends of these bundles insert directly into the basal lamina. Individual fibrils are morphologically identical with the microfibrils that are a component of true elastic fibers [6, 7]. Indeed, some dermal microfibril bundles have been traced to connections with morphologically distinct elastic fibers thus documenting a direct connection between the basal lamina and elastic fibers in the dermis via these structures [8]. Typical collagen fibers are the third fibrous component in the sub-basal lamina area. These are randomly oriented and are most commonly found as single fibers or occasionally in groups of several fibers. Collagen fibers do not attach directly to the basal lamina or to other junctional structures as yet identified. BIOCHEMICAL COMPOSITION OF BASEMENT MEMBRANE WITH PARTICULAR REFERENCE TO THE EPIDERMAL-DERMAL JUNCTION Before concentrating on the epidermal-dermal junction, we will first review current knowledge of biochemical composition of basement membranes in general [9,10]. Basement mem­ branes are composed of collagenous and noncollagenous com­ ponents which are tabulated below (Table). Basement Membrane Collagens Current evidence indicates that the basement membrane collagens are distinct from the interstitial collagens and can be subdivided into 3 groups, designated type IV, type V (AB collagen), and 7S collagen. Type IV collagens FIG Epidermal-dermal junction in region of a hemidesmosome. To­ Type IV collagen is composed of 3 polypeptide chains that noftlaments (TF). Attachment plaque (AP). Plasma membrane (PM). form a macromolecule with triple helical domains similar to Subbasal d ense plaque (SBDP). Anchoring ftl aments (A}. Lamina other collagens. However, the constituent polypeptide chains of Iu cida (LL). Basal lamina (BL). Anchoring fibril (AF). Collagen fib er type IV collagen are larger than other collagens and are disul­ (COL}. Dermal microfibril bundle (MF). fide-linked. In addition, nonhelical sequences constitute a larger TABLE I. Composition of basement membrane Basement membrane Moi.Wt. Cutaneous localization Source Basement membrane co mponents (BM) (K) distribution Presence Ultrastructural Collagenous T ype IV collagens >400 Lt l (IV} 160 Mouse EHS sar coma Ubiquitous + Basal lamina a 2 (IV) 140 Kidney and ocular BM Pro a 1 (IV} 185 Pro a 2 (IV) 170 Fetal membranes T ype V collagens 300 a A 100 Fetal membranes Vascular, + ? a B 100 muscle, skin, muscle BM aC bone, lung 7S collage n 360 Mouse EHS sarcoma Ubiquitous + ? kidney, ocula1· BM fetal membranes N onco llagenous Bullous pemphigoid antigens Epidermal 20, 9.2 Skin Skin, other + Lamina Iucida Urinary 19 Urine sq. epithelial High mol. wt. 220 Epidermal cell culture Lam in ins Soluble laminin 800-1000 EHS sarcoma Ubiquitous + Lamina Iucida Subunits 220 440 Insoluble laminin EHS sarcoma ? ? ? Hepanin sulfate pro­ 750 EHS sarcoma Ubiquitous Leoglycan + ? Fibronectin 440 Plasma, Ubiquitous + Lamina Iucida Subunits 220 Fibroblastic cells Amyloid P -compo­ plus dermis Kidney Kidney ? nent ? Jan. J982 BIOCHEMICAL COMPOSITION OF THE EPIDERMAL-DERMAL JUNCTION 3 portion of type IV collagen than other collagens as indicated by have been designated pro-a 1 (IV) and pro-ex2 (IV) to indicate the glycine content which is less than the 1/3 dictated by the their precursor relationship to the smaller tissue forms that are Gly-X- Y helix sequence. Distinctive differences are also evident now termed a 1 (IV) and a 2 (IV) [26- 28]. It is believed that in the content of other amino acids and in the posttranslational these represent the major alpha chain-like components of type hydroxylation and glycosylation of type IV collagen. The ratios IV collagen although other minor components have been iden­ of 3- to 4-hydroxyproline, of total hydroxyproline to proline and tified but not yet characterized [28]. hydroxylysine to lysine are greater in type IV collagen and serve as distinguishing featmes. Type IV collagen also has a Type V (AB) collagens high carbohydrate content, most of which is present as disac­ chrides containing glucose and galactose bound to hydroxyly­ Concomitantly, 2 groups of investigators [29,30] discovered 2 sine.
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