Christian Rainer

Matrix Metalloproteinases 9 and 2 Are Necessary for the Migration of Langerhans Cells and Dermal Dendritic Cells from Human and Murine Skin

Dendritic cells migrate from the skin to the draining lymph nodes. They transport immunogenic MHC-peptide complexes, present them to Ag-specific T cells in the T areas, and thus generate immunity. Migrating dendritic cells encounter physical obstacles, such as basement membranes and collagen meshwork. Prior work has revealed that matrix metalloproteinase-9 (MMP-9) contributes to mouse Langerhans cell migration. In this study, we use mouse and human skin explant culture models to further study the role of MMPs in the migration and maturation of skin dendritic cells. We found that MMP-2 and MMP-9 are expressed on the surface of dendritic cells from the skin, but not from other sources. They are also expressed in migrating Langerhans cells in situ. The migration of both Langerhans cells and dermal dendritic cells is inhibited by a broad spectrum inhibitor of MMPs (BB-3103), by Abs to MMP-9 and -2, and by the natural tissue inhibitors of metalloproteinases (TIMP), TIMP-1 and TIMP-2. Inhibition by anti-MMP-2 and TIMP-2 define a functional role for MMP-2 in addition to the previously described function of MMP-9. The importance of MMP-9 was emphasized using MMP-9-deficient mice in which Langerhans cell migration from skin explants was strikingly reduced. However, MMP-9 was only required for Langerhans cell migration and not maturation, since nonmigrating Langerhans cells isolated from the epidermis matured normally with regard to morphology, phenotype, and T cell stimulatory function. These data underscore the importance of MMPs, and they may be of relevance for therapeutically regulating dendritic cell migration in clinical vaccination approaches.

Expression of the C-C chemokine MIP-3α/CCL20 in human epidermis with impaired permeability barrier function

Abstract: External assault to the skin is followed by an epidermal response including synthesis of DNA, lipids, cytokines and migration of antigen presenting cells. MIP‐3α (CCL20, LARC, Exodus‐1, Scya20) is a recently described C‐C chemokine, predominantly expressed in extralymphoid tissue, which is known to direct migration of dendritic cell precursors and memory lymphocytes to sites of antigen invasion. We assessed the expression of MIP‐3α in human skin using semi‐quantitative polymerase chain reaction. In vivo, MIP‐3α mRNA was constitutively expressed at low levels in untreated human epidermis. After acute disruption of the epidermal permeabiltiy barrier MIP‐3α mRNA was upregulated in the epidermal fraction, whereas dermal MIP‐3α mRNA levels remained unchanged. In vitro, MIP‐3α was increased in cultured keratinocytes treated with IL‐1α and TNF‐α and was present in immature and mature dendritic cells, THP‐1 monocytic cells and activated T cells. Finally, skin biopsies from patients with psoriasis, contact dermatitis and mycosis fungoides showed abundant expression. In biopsies from atopic dermatitis and graft vs. host disease a weak signal was present, whereas no expression was found in scleroderma and toxic epidermal necrolysis. We conclude that regulation of MIP‐3α mRNA is part of the epidermal response to external assault. Its upregulation may represent a danger signal for increased immunosurveillance in barrier disrupted skin and inflammatory skin conditions with impaired barrier function to counteract potential antigen invasion.

Successful transplantation of three tissue-engineered cell types using capsule induction technique and fibrin glue as a delivery vehicle.

Recent advances in cell biology and tissue engineering have used various delivery vehicles for transplanting varying cell cultures with limited success. These techniques are frequently complicated by tissue necrosis, infection, and resorption. The purpose of this study was to investigate whether urothelium cells, tracheal epithelial cells, and preadipocytes cultured in vitro could be successfully transplanted onto a prefabricated capsule surface by using fibrin glue as a delivery vehicle, with the ultimate goal for use in reconstruction. In the first step of the animal study, tissue specimens (bladder urothelium, tracheal epithelial cells, epididymal fat pad) were harvested for in vitro cell culturing, and a silicone block was implanted subcutaneously or within the anterior rectus sheath to induce capsule formation. After 6 to 10 days, when primary cultures were confluent, the animals were re-anesthetized, the newly formed capsule pouches were incised, and the suspensions of cultured urothelia cells (n = 40), tracheal epithelial cells (n = 32), and preadipocytes (n = 40) were implanted onto the capsule surface in two groups, one using standard culture medium as a delivery vehicle and the second using fibrin glue. Histologic sections were taken, and different histomorphologic studies were performed according to tissue type. Consistently in all animals, a highly vascularized capsule was induced by the silicon material. In all animals in which the authors used fibrin glue as a delivery vehicle, they could demonstrate a successful reimplantation of cultured urothelium cells, tracheal epithelial cells, or preadipocytes. Their animal studies showed that capsule induction in combination with fibrin glue as a delivery vehicle is a successful model for transplantation of different in vivo cultured tissue types.

Free flap reconstruction of the foot.

Free flap reconstruction of the foot has been widely performed in the last 20 years, but choice of a free transferred substitute for the soft tissue of the particular defect remains controversial. The authors present a series of 77 free flaps to the foot performed in 68 patients during October 1976 and September 1997. Long-term follow-up ranged from 12 months to 18 years (median, 44.4 months). Seventy-three flaps were transferred successfully (95%). The indications for a specific flap depended on the localization and extension of the foot defect. In weight-bearing areas the authors favored the use of a muscle flap covered with a split-thickness skin graft; the latissimus dorsi muscle was used primarily. This study shows a lower ulceration rate in muscle flaps covered with split-thickness skin grafts than in fasciocutaneous flaps in weight-bearing areas (27% vs. 60%). In nonweight-bearing areas, fasciocutaneous flaps were the best choice. In this series, the lateral arm flap was applied most often. The authors recommend free fascial flaps (serratus fascial flap or radial forearm fascial flap) covered by split- or full-thickness skin grafts for coverage of the malleolar region as well as coverage of exposed tendons of nonweight-bearing regions. Proper tailoring of the flap and postoperative care are very important to maintain a result without ulceration, as is avoiding having the suture line cross a weight-bearing area. Tactile sensation does not seem to be essential.

Does a superficial musculoaponeurotic system exist in the face and neck? An anatomical study by the tissue plastination technique.

&NA; An exact knowledge of the subcutaneous layers in the different regions of the face and neck is important in several surgical disciplines. In the parotid region, a superficial musculoaponeurotic system (SMAS) has been described. The existence of a SMAS as a guiding structure for the surgeon in the other regions of the face and neck has been discussed but is controversial. Therefore, the authors investigated the development of the subcutaneous connective‐tissue layers in the different facial regions and in the neck. They studied these regions in 22 human fetuses using the technique of plastination histology and in three newborn and three adult specimens using sheet plastination. In addition, they dissected the neck and face in 10 fresh adult cadavers to identify the SMAS as in the surgical situation. The results show that no SMAS could be detected in any facial regions other than the parotid region. In the parotid region, it is thick and attached to the parotid sheath. However, it becomes very thin, discontinuous, and undissectable in the cheek area. No SMAS can be found in the neck, in which the authors are the first to describe a fascia covering both sides of the platysma. This fascia has close topographical connections to the subcutaneous layers of the adjoining regions. On the basis of these findings, the surgical pathways have to be defined regionally in the face. A “platysma fascia” can be considered as a surgical landmark in the neck. Therefore, the authors conclude that it is not justified to generalize a SMAS as a surgical guiding structure. (Plast. Reconstr. Surg. 111: 664, 2003.)

New technique for scarless umbilical reinsertion in abdominoplasty procedures

The most visible scar in the conventional abdominoplasty procedure or TRAM flap donor site closure is the scar around the reinserted umbilicus. In an attempt to increase the aesthetic outcome, the authors have introduced a new technique of umbilical reconstruction and reinsertion during abdominoplasty avoiding any paraumbilical scar, which results in a more natural appearance in that area. This new technique, potential pitfalls, and long-term results are reported.

Anterior neck reconstruction with pre-expanded free groin and scapular flaps

To improve aesthetic and functional outcomes in the reconstruction of severe anterior neck burn deformities and to reduce donor-site morbidity, pre-expansion of free-flap donor sites was performed in eight patients. In the first stage of reconstruction, the tissue expander was placed and gradually inflated over a period of 6 weeks. In the second stage, the anterior neck scar was resected up to the limits of the aesthetic unit of the neck, radical release of neck contracture was achieved by transection of contracted platysma muscle, and immediate coverage with a pre-expanded groin or scapular free flap was performed. The early postoperative course was uneventful. Physical therapy was started 1 week after the reconstruction. Long-term follow-up (mean, 4 years) of patients who underwent reconstruction of extensive neck burn deformities demonstrated good aesthetic and functional results. The advantages and drawbacks of using pre-expanded free flaps in the treatment of neck burn contractures are discussed.

Clinical experience and indications of the free serratus fascia flap: a report of 21 cases.

&NA; The free “serratus fascia” flap as a free flap was first described by Wintsch and named a free fascia flap of gliding tissue; however, it has not yet been given a distinct name. The particular advantages of this flap consist of an easy access and a low donor‐site morbidity without functional deficit. Additionally, it may be designed very variably and molded even three‐dimensionally as a tendon wraparound flap or folded to fill up cavities. In our clinic, we used this flap in 21 patients for distinct indications and in 7 patients as a vascular graft in fingers or great toe with a minimal adjacent layer of gliding tissue around the vessels for the treatment of cold intolerance after finger replantation or severe finger or toe trauma. In the other cases, this versatile flap served for the coverage of traumatically exposed tendons or bones at the extremities, covered with a skin graft. Eighteen flaps survived completely, whereas 3 flaps developed partial or superficial necrosis. Only once did a major complication by unintentional sacrification of the long thoracic nerve during flap harvesting occur, resulting in a wing scapula. We recommend this flap for defect cover at sites where a thin vascularized gliding layer for defect cover is needed, especially in distal extremities with exposed tendons or nerves, and present the current indications in discussing our experiences. (Plast. Reconstr. Surg. 102: 1939, 1998.)

Use of new bioabsorbable tacks and a tackshooter in cranial bone osteofixation saves operative time.

A new device (a tackshooter) to apply bioabsorbable tacks in craniofacial surgery has been developed. This new device was used in 15 children who underwent various cranioplasty procedures to demonstrate its reliability and simple technical application in cranial bone osteofixation. Bone segments were fixed together and to the cranial bones using Biosorb plates and tacks. Stable and secure fixation was obtained intraoperatively, with reduced operative time (10–15%) compared with earlier use of plates and screws. However, its use in very thin bone (<1 mm thick) is very limited because of bone fragility. In conclusion, use of tacks and a tackshooter reduces operative time, risk of infection and blood loss, and consequently costs. It is therefore very useful in selected craniofacial cases.

Sebaceous carcinoma of the eyelid: a rarity worth considering

The sebaceous carcinoma is a very rare malignant tumour primarily found in the area of the eyelid. Most of these carcinomas originate in the tarsal meibomian glands although they may in extremely rare cases originate in the glands of Zeis of the eyelashes or the sebaceous glands of the caruncle.1 The periorbital primaries are reported to behave aggressively with the tendency to metastasise early with a significant mortality in most series.2 In many cases correct diagnosis of a sebaceous carcinoma of the eyelid is delayed not only as a result of the rarity of this tumour but also because of its ability to masquerade as a variety of other eye conditions such as chalazion or chronic blepharoconjunctivitis. A high index of suspicion is vital if these tumours are to be adequately treated. We present a case of sebaceous carcinoma and discuss the clinical behaviour, the diagnosis, and the differential diagnosis difficulties as well as the therapy. A 78 year old patient presented with a localised inflammation in the centre of the right upper eyelid. Under local antibiotic therapy for 6 weeks …