Multiple Roles for Elastic Fibers in the Skin
Department of Biochemistry, University of Texas Health Center at Tyler, Tyler, Texas (BS,RLA) and Department of Poultry Science, North Carolina State University, Raleigh, North Carolina (CHH)
Correspondence to: Barry Starcher, Department of Biochemistry, University of Texas Health Center at Tyler, 11937 US Highway 271, Tyler, TX 75705. E-mail: barry.starcher{at}uthct.edu
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Summary |
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Key Words: elastic fibers skin follicle
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Introduction |
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The skin is the largest single organ of the vertebrate body, covering its entire surface, along with accessory organs such as various glands, nails, and hair or feathers. With the exception of birds, which are covered with feathers, most animals are covered with hair over much of the body. With certain unique exceptions, hair and feathers perform similar roles physiologically and share many anatomical similarities. Both hair and feathers are enclosed by a follicle or sheath derived primarily from epithelial cells. Movement of feathers is directed by multiple bands of smooth muscle attached to the follicles by elastic fibers, whereas the movement of hair is directed by a single arrector pili muscle, also linked to the hair follicle by elastic fibers. Although anatomically the arrangement of the smooth muscleelastic fiber network is quite different between hair and feathers, we suggest that the mechanical performance of elastic fibers in the skin may be the same for almost all animals.
Traditionally, dermal fibroblasts have been considered to be the source of the elastic fibers in the skin (Pieraggi et al. 1985; Sephel and Davidson 1986
). Recent studies have indicated that elastic fibers in the skin of mice are derived not from fibroblastic cells but from epithelial-like cells surrounding the hair follicle (Starcher et al. 1999
). This observation raises the possibility that elastic fibers in the skin of all animals are follicle associated and have a role in hair or feather movement, as well as maintenance of skin elasticity. The present studies were designed to examine more closely the relationship between elastic fibers and feather or hair follicles.
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Materials and Methods |
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Desmosine analysis was used in each of the various skin samples in this study as a method for measuring the elastin content of the skin. After removing the hair, a 4-mm biopsy punch was obtained from each fixed skin and placed in a secure-lock microfuge tube. The sample was hydrolyzed in 500 µl of 6 N HCl at 105C for 24 hr. The hydrolysate was evaporated to dryness, re-dissolved in 200 µl water, and microfuged to remove insoluble material. Twenty µl was removed for desmosine analysis by radioimmunoassay (Starcher and Conrad 1995), and 1 µl was used for protein determination using a ninhydrin-based assay described previously (Starcher 2001
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Results |
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Mammalian Skin Elastin
The investigated animals were divided into two broad categories, one in which the coat consists of single uniform hairs, and the other in which the coat consists of major hair follicles surrounded by fine hair or wool. Examples of each are illustrated below.
Single (Primary) Hair Follicles
The distinguishing feature about the hair in this type of skin is that the follicles are not arranged in groups but stand as individual hair follicles, each independently connected to an arrector pili muscle. Humans, mice, deer, cows, horses, pigs, and some dogs typically have this type of hair arrangement, with single, uniform hair follicles, each in communication with other hair follicles through long elastic fibers that extend out through the matrix. The deer was particularly convenient for these studies, because the elastic fibers surrounding the hair follicles in deer are very large and more densely packed than in any of the other mammals we investigated. A sagittal section of deer skin, stained for elastin and immunostained for smooth muscle actin, is shown in Figure 2A. The dark-purple elastic fibers are seen lying parallel to the epithelium and extending from one hair follicle to another. In a single sagittal section, it was impossible to establish origins or attachments because of the wavy nature of the fibers and the offset of the hair follicles. The pili muscle, stained red, lies in close proximity to the hair follicle and again, as was noted above, it was difficult to discern whether the elastic fibers were associated with the pili muscle. With enface sectioning, the elastic fibers in deer skin can usually be viewed in their entirety, connecting follicle to follicle (Figure 2B). The pili muscle can be seen in cross-section aligned along each associated follicle. The elastic fibers are derived from cells lining the follicle and not from other areas of the matrix or the pili muscle. They are not unidirectional but diverge in many directions, connecting to multiple hair follicles. The pili muscle, as illustrated from a section of long-tail macaque monkey skin (Figure 2C), is attached to the matrix just under the basement membrane by elastic fibers that appear to extend from the end of the pili muscle and become embedded in the collagen-rich matrix. The pili muscle extends down the entire length of a hair follicle, where it attaches to the follicle below the sebaceous glands, and along the apex of the follicle, as illustrated with deer skin (Figure 2D). At both sites of attachment, the pili muscle undergoes a transition from smooth muscle to elastic fibers, which anchor the muscle at both ends. This arrangement was observed in almost all animal skins that we investigated.
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We also examined several samples of human skin from different anatomical areas and from subjects of varying ages. Because the samples from older subjects had been exposed to UV irradiation, the solar elastotic masses of elastin in these samples prevented us from determining any individual elastic fiber interactions. One sample, from an 8-month-old subject, showed no pathology and was used for these studies. It was evident that human skin elastic fiber orientation was different in many respects from that of the other animals that we investigated. Elastic fibers were not confined to the upper dermis as observed with most animals but appeared uniformly distributed throughout the entire dermis, as shown in a sagittal section (Figure 3A). Although a few of these fibers were short and appeared fragmented, most were long, relatively straight, and parallel to the epithelium. If the same skin was sectioned in cross-section, the fibers that all appeared to be very short were actually cross-sections of elastic fibers and again illustrate how straight and aligned the fibers were (Figure 3B). This is contrasted to a sagittal section of adult skin showing significant elastosis and irregular elastic fibers (Figure 3C). When viewed enface, the juvenile skin showed elastic fibers associated with a hair follicle in a manner similar to other animals (Figure 3D). Hair follicles were relativity far apart, and it was not possible to obtain a section containing several follicles. Although some elastic fibers could be observed surrounding a single hair follicle and appeared to be derived from that follicle, we were unable to establish the hair follicle as the main source of the elastic fibers observed throughout the dermis in human skin.
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Multiple (Primary and Secondary) Hair Follicles
Wool-bearing animals and animals with fine fur have two or more dissimilar types of hair follicles. Included in this group are the rabbit, sheep, fox, squirrel, raccoon, some dogs, and many other mammals. Multiple-follicle skin is illustrated with Gomori's trichrome staining of a section of rabbit skin showing the distinctive arrangement between two different types of hair follicles (Figure 4A). The large-diameter primary hair follicle is partially encircled by clusters of smaller secondary follicles representing the wool hair of these animals. The pili muscle extends down through the matrix and connects only to the primary hair follicle. The attachment is made through elastic fibers in the same manner as illustrated previously (Figure 2D). Virtually all of the elastic fibers in the upper half of the dermis are derived from the primary follicle and extend out and enclose the bundles of secondary hair follicles as illustrated in an en face section (Figure 4B). Sections from deeper in the rabbit dermis indicate that the secondary follicles are interconnected at the apex by fine elastic fibers, which tie into the main follicle that is surrounded by heavy elastin fibers embedded in a collagen-rich matrix (Figure 4C).
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The skin of fox contains three distinct sizes of hair follicles, as illustrated in Figure 4H. Elastic fibers interconnect the small secondary follicle bundles and tie into a larger follicle at the head of each of these bundles (Figure 4I) This follicle is in turn connected through larger elastic fibers to the primary hair follicle. Only the primary follicle is attached through elastic fibers to the pili muscle (Figure 4H).
The elastin arrangement in the skin of the raccoon is similar to that in fox skin, with a primary hair follicle bound on one or two sides by a bundle of smaller secondary follicles (Figure 4J). Each secondary follicle is surrounded by fine elastic fibers that connect to the primary follicle. The primary follicles extends deeper into the dermis than the secondary follicles and, when sectioned below these smaller follicles, it can be seen that only the primary follicle is linked directly to the large pili muscle through elastic fibers (Figure 4K).
The skin from squirrels also has more than one type of hair follicle. The elastin aspect of the dermis in the squirrel is very shallow, inasmuch as the hair follicles penetrated less than one-fifth of the depth of the skin. Most of the elastic fibers are concentrated in the lower half of the primary follicle and, when viewed enface, appear as a mass of very fine elastic fibers extending in all directions to contact other follicles (Figure 4L). When viewed at higher power, the elastic fibers were all found to originate from the primary hair follicle (Figure 4M).
Hair Follicles without Pili Muscle Regulation
We investigated hair follicles at sites where hair movement might not be under smooth muscleelastic fiber control, such as a mouse or rabbit ear where the skin is tightly affixed to the cartilage matrix and the whole ear moves, but perhaps not the hair independently. Figure 5A illustrates an enface section of a hamster ear stained for elastin, showing the hair follicles and associated sebaceous glands. Regardless of the orientation of different sections, we found no elastic fibers associated with the hair follicles. The same observation was made for mouse ear skin. In both instances, almost all the elastin present in the ear was part of the elastic cartilage. However, this observation was not consistent with regard to the rat or rabbit ear, where at least some of the hair follicles were surrounded by the normal elastic fiber network (Figure 5B). In the rat, long elastic fibers extended from some hair follicles to connect with other follicles. Another site investigated was the muzzle, or cheek area, where the large, stiff tactile hair (vibrissae) stand out from other hair. A whisker hair follicle of a mouse stained for elastic fibers is shown in sagittal section in Figure 5C. No visible elastic fiber network was observed adjoining the hair follicle, and it appeared that there was no pili muscle associated with the tactile hair follicle. Enface sections also confirmed the paucity of elastic fibers and showed the follicle to be embedded in a matrix rich in skeletal muscle (Figure 5D). It appeared that small, thin elastic fibers were present in the region immediately surrounding the hair shaft, as shown by the arrow in Figure 5D. The role of these small, fine fibers was not evident.
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Discussion |
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Avian skin is an exaggerated example of how elastic fibers in the skin have a primary role in the movement of a skin covering. They perform this function by connecting feather follicles to large smooth muscle bundles with an elastic fiber linkage. For feathers some distance apart, a massive segmented smooth muscleelastic fiber cable spans the distance and connects the follicle at both ends with elastic fibers. In our study we found no evidence of additional, ordered or randomly placed, elastic fibers distributed throughout the avian skin that might contribute to skin elasticity. It is quite possible, however, that the smooth muscleelastin network, which covers the entire skin area, provides a degree of stretch and recoil to the skin, with the feather follicles performing the role of anchor points.
The elastic fibers in the skin of animals with hair perform essentially the same function as the elastic fibers found in avian skin. However, the arrangement has been modified to meet the lesser requirements for hair movement. A single, slender arrector pili muscle has replaced the substantial arrector, repressor, and depressor muscles seen in avian skin. The forces required to pull a hair upright are much lower than those required to raise and lower and/or maintain a feather in place during flight. In both instances, however, an elaborate elastic fiber network surrounding the follicle is involved in the attachment of the muscles. Elastic fibers also emanate from the sub-basement membrane end of the pili muscle in haired animals to anchor the pili muscle to the matrix, whereas in avian species, the muscle connects at each end to adjacent feather follicles through this elastin network.
The alternating smooth muscle bundleelastic fiber bundle found in avian species, which connects feather follicles that are far removed from each other, does not seem to have a counterpart in haired animals. In animals with hair, with a few possible exceptions, each hair follicle is connected to other follicles directly, with numerous elastic fibers originating at many sites up and down the hair follicle. Smooth muscle does not appear to have a role in this process. The physical site or other proteins involved in the elastic fiber attachment to the follicular or smooth muscle cells is unknown.
For animals with wool or fur, the system has been efficiently designed such that only one pili muscle is required to stimulate the adjacent bundles of smaller secondary hair follicles. This is accomplished through a single primary hair follicle, from which the majority of the elastic fibers originate, and to which the pili muscle is attached. Fine elastic fibers arising at the apex of the secondary follicles connect them to each other and, subsequently, all connect to the primary follicle. In this manner, a contraction or signal carried to the primary follicle by a single pili muscle could be transmitted to the numerous secondary follicles.
The pattern of elastic fibers in the skin of humans suggests a different role, and perhaps cell of origin, than all other animals we investigated. A possible exception is the pig, which appears to have some similarities in location and function. Elastic fibers in human skin are not concentrated in areas of hair follicles but are dispersed throughout the entire dermis in comparable concentrations and distributions.
There is no doubt that individual hair follicles are associated with elastic fibers in much the same manner as in other animals, yet the sheer mass and distribution of most of the elastic fibers suggests other sources of origin, presumably fibroblasts, throughout the dermis. As elastic fibers age and/or are exposed to solar damage, the fibers lose definition and can eventually become an amorphous mass, as observed in Figure 3C. These masses occur throughout the dermis and appear to have no relationship with hair follicles. The difference observed in human skin was not related to the primate order because the three other primate skin representatives we studied maintained the same elastic fiberhair follicle relationship that we observed in most other animals.
The elastic fiberhair follicle pattern is not the same for skin on all parts of the animal body. For example, hair on the ear of a mouse and hamster does not appear to have detectable elastic fibers associated with the hair follicles. This observation could be explained by the lack of regulated hair movement on the ears of these animals. The animals move the entire ear but not the individual hairs on the ear. Another example is the tactile hairs (whiskers) that are found on the cheek or muzzle of animals. These follicles are encased in skeletal muscle and are voluntarily moved by the animal. We did not find the typical elastic fiber network at this site.
The hair cycle occurs in three stages: anagen, catagen, and telogen. During anagen, the hair follicle penetrates the dermis, and in some animals, the dermal papilla reaches almost to the carnosus muscle layer. After a period of growth, the hair follicle goes into a resting state or catagen, where the entire lower half (inferior region) of the follicle regresses to a point just below the attachment of the pili muscle. Do elastic fibers grow out from the cells lining the follicle in the inferior region? If this were true, complete removal of the old elastic fiber network would be required and a new system installed with each growth phase of the hair cycle. This possibility does not seem to be the case, because elastin fibers are concentrated just below the area of the pili attachment, and no elastic fibers are observed below this point in the inferior region. This conclusion was reached for all species of animals investigated except human and pig. In human skin, and to a lesser degree, pig skin, the elastic fibers lie as parallel fibers the entire depth of the dermis. This includes the inferior region of the hair follicles and again demonstrates the uncharacteristic nature of human skin, as opposed to the skin of other species.
Another note of interest was the chronological order of appearance of elastic fibers in the dermis of the non-human skin. In chicken skin, the elastic fibers connecting the follicles appeared 23 days prior to hatch. At this time, the feathers have developed and the birds hatch fully feathered. In contrast, when we look at mouse skin, in which the animals are born without visible hair, there are no elastic fibers present in the skin of the fetal mice except those associated with blood vessels or the carnosus muscle layer. Dermal elastic fibers emanating from the hair follicles are first evident at 5 days after birth. This corresponds to the time that hair first appears on the skin surface of these animals.
In summary, our studies indicate that for avians and most mammals, elastic fibers in the skin are predominantly allied with feather or hair follicles and the associated smooth muscle bundles, suggesting that movement or maintaining position of the skin covering is the principal role for elastic fibers in the skin. Hair follicles associated with skeletal muscle do not appear to have a comparable elastic fiber arrangement. The elastic fiber origin and arrangement in human skin is atypical compared with other animals and may have a more prominent role in stretch and recoil and maintenance of skin integrity.
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Footnotes |
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Literature Cited |
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