The expression pattern of adhesion molecules is characteristic for each cell population and changes during the maturation process of a cell [16]. 2.1. involved offers fascinating novel therapeutic options in the prevention and treatment of skin rejection after VCA. 1. Introduction Acute skin rejection is usually a frequent challenge, and long-term immunosuppression is usually a necessity in vascularized composite allotransplantation (VCA) [1]. The toxicity profile of such a drug treatment includes metabolic side effects, opportunistic infections, malignancy, and organ damage [2C6]. This illustrates the need for immunosuppressive-sparing protocols in order to limit side effects of this quality-of-life improving process and widen the indications for VCA. The infiltration of alloantigen specific T cells into the skin allograft has been identified as a central element of acute skin rejection in VCA [7, 8]. Histologically, the appearance of skin rejection (+)-α-Tocopherol shares many common features with inflammatory skin diseases and may be difficult to distinguish [9, 10], suggesting that underlying immunological mechanisms might be comparable in some aspects. In inflammatory skin conditions, T-cell recruitment to the skin is orchestrated by a multitude of adhesion molecules, cytokines, and chemokines [11]. In part, this concept of inflammation and immune activation holds also true for the initiation and progression of allograft rejection in solid organ transplantation (SOT) [12]. A mechanism currently discussed to be involved in the development of chronic allograft rejection is the formation of lymphoid neogenesis and tertiary lymphoid organs (TLOs) in the transplant [13C15]. The mechanisms and dynamics of skin allograft rejection have been partially understood and remain the subject of numerous trials aiming at a better understanding of the pathophysiology and novel and targeted drug development. We herein review the molecular events and key players of inflammation as well as new therapies with particular regard to skin inflammation and allograft rejection in SOT and discuss them in the light of acute and chronic skin allograft rejection of VCAs. 2. Adhesion Molecules: Anchors for Lymphocyte Recruitment to the Skin Adhesion molecules play a crucial role in the function of immune cells. They are the central actors helping leukocytes to immediately convert from an inactive, nonsticky status to an adhesive status, though permitting adhesion (+)-α-Tocopherol to the vascular endothelium with transmigration to inflamed tissues. Further they support cell-cell interactions through various homophilic and heterophilic interactions and have the ability to transmit costimulatory signals to the interacting cells. The expression pattern of adhesion molecules is characteristic for each cell population and changes during the maturation process of a cell [16]. 2.1. Adhesion Molecule Families (1) Selectins 3 subtypes of selectins, characterized through their N-terminal lectin domain, are defined (+)-α-Tocopherol [17, 18]: E-selectin is mainly expressed by activated endothelial cells, whereas endothelium of noninflamed tissue does not express E-selectin. Potent stimuli of E-selectin expression are IL-1 and TNF [19]. The P in P-selectin stands for platelet, but P-selectin is also expressed in activated endothelial cells, where it is stored in Weibel-Palade bodies [20] and is released upon stimulation [21]. In contrast to E- and P-selectins, L-selectin is constitutively expressed on lymphocytes, neutrophils, and monocytes and is known to play a crucial role Rat monoclonal to CD4.The 4AM15 monoclonal reacts with the mouse CD4 molecule, a 55 kDa cell surface receptor. It is a member of the lg superfamily,primarily expressed on most thymocytes, a subset of T cells, and weakly on macrophages and dendritic cells. It acts as a coreceptor with the TCR during T cell activation and thymic differentiation by binding MHC classII and associating with the protein tyrosine kinase, lck in homing of lymphocytes to secondary lymphoid tissues through binding to its counter-receptor addressin, which is expressed by high-endothelial venule cells [22, 23]. However, there is now growing evidence that all three types of selectins contribute to leukocyte extravasation in the skin with overlapping effect. E- and P-selectin seem to play the most important role in leukocyte homing into the skin [24]. This idea is supported by the failure of monoselectin antagonists and the success of pan-selectin agonists in targeting leukocyte extravasation [25, 26]. All types of selectins bind to carbohydrate ligands such as the tetrasaccharides Sialyl-Lewis-x or P-selectin glycoprotein ligand-1 (PSGL-1) [27, 28]. (2) Integrins and the Ig Family Leukocytes (neutrophils, monocytes, lymphocytes, and natural killer cells) express the integrins lymphocyte function-associated antigen-1 (LFA-1) and Mac-1 (both sharing a common (IFN-are significantly upregulated in psoriatic skin lesions and thus responsible for the typical intraepidermal aggregation of neutrophils. CCL2/MCP-1 and CCL5 are responsible for attracting predominately monocytes and T cell subsets, and CXCR3 ligands attract Th1 cells [103]. The expression of cytokines.
The expression pattern of adhesion molecules is characteristic for each cell population and changes during the maturation process of a cell [16]
