Type XVI Collagen is Expressed in Factor XIIIa+ Monocyte-Derived Dermal Dendrocytes and Constitutes a Potential Substrate for Factor XIIIa

Abstract

We have previously reported that connective tissue cells in the superficial dermis preferentially express alpha1(XVI) collagen rather than those in the lower dermis. Double immunofluorescence labeling using the antibodies for alpha1(XVI) collagen and factor XIIIa (plasma transglutaminase), which is a marker of dermal dendrocytes, demonstrated that both antibodies reacted with the same cells in the superficial dermis of normal skin as well as the lesional skins of dermal dendrocyte-related disorders, dermatofibroma, and psoriasis. Dermal dendrocytes are considered to be established by a culture of peripheral blood monocytes in the presence of granulocyte macrophage-colony stimulating factor and interleukin-4. Reverse transcription--polymerase chain reaction, metabolic labeling, and immunofluorescence studies demonstrated that treatment of CD14+ peripheral blood monocytes with granulocyte macrophage-colony stimulating factor/interleukin-4 over a period of 8 d resulted in the induction of alpha1(XVI) collagen as well as factor XIIIa. The physiologic significance of colocalization of alpha1(XVI) collagen and factor XIIIa in the tissue and their coordinate induction in CD14+ monocyte-derived dendritic cells in vitro was studied. Considerable incorporation of [3H]putrescine by factor XIIIa into recombinant noncollagenous domain (NC) 11 but not into collagenous domain (COL) 1.NC1 domain of the alpha1(XVI) polypeptide was found. Incubation of recombinant NC11 of alpha1(XVI) polypeptide with factor XIIIa in vitro produced a covalent cross-linking complex on sodium dodecylsulfate-polyacrylamide gel electrophoresis. The results indicate that alpha1(XVI) collagen is constitutively expressed by most dermal dendrocytes in the skin and dendritic cells differentiated from peripheral blood monocytes in vitro. Type XVI collagen is expressed in factor XIIIa+ dermal dendrocytes and may form an intermolecular cross-linking through NC11 domain by the reaction catalyzed by factor XIIIa contributing to the structural integrity of factor XIIIa+ dendritic cell-rich tissues.

Factor XIII and inflammatory cells

“…A significant elevation of FXIII-A mRNA and protein level was observed during monocyte/macrophage differentiation in cell culture [30,31] and TG-2 also became up-regulated [32][33][34]. Induction of in vitro differentiation of monocytes into antigen presenting dendritic cells resulted in highly elevated FXIII-A expression [35][36][37].…”

“…However, a few studies indicated that in cultured cells it could be translocated to the surface [26,30,39]. The appearance of FXIII-A in the culture medium suggested its secretion by dendritic cells [37]. However, dying or dead cells may be the source of cell surface associated or soluble phase FXIII.…”

COL16A1 (collagen, type XVI, alpha 1)

“…It is synthezised by dermal fibroblasts, smooth muscle cells (Grässel et al, 1996), dermal dendrocytes and dendritic cells in the skin (Akagi et al, 2002), articular and costal chondrocytes (Kassner et al, 2003), endometrial stromal cells (Tierney et al, 2003), basal dermal and oral keratinocytes (Grässel et al, 1999), bone marrow derived mesenchymal stem cells (Grässel et al, 2009), neurons from the dorsal root ganglion (Hubert et al, 2007), glioblastoma/astrocytoma cells (Senner et al, 2008) and intestinal myofibroblasts (Ratzinger et al, 2010). Collagen type XVI is further expressed in the limbal stem/progenitor niche which comprises clusters of cells in the basal epithelium.…”

The role of factor XIII-A in the development of inflammatory skin lesions

“…Change in the FXIII-A-positive dermal dendrocytes is characterized by intense cytoskeletal reorganization resulting in many cellular functions and improvement of tensegrity. The intracellular activity of FXIII-A may be responsible for proliferation, differentiation, migration, survival and excessive inflammatory cytokine secretion of dermal dendrocytes [5,6,8,9,12,15].…”

“…FXIII-A, as a potential active subunit is also present in the cytoplasm of platelets, monocytes, macrophages, dendritic cells, chondrocytes, osteoblasts, and osteocytes. It can be detected from the early stage of monoblasts in the bone marrow via blood monocytes to the connective tissue macrophages [4][5][6][7][8][9][10][11]. FXIII-A is considered as a positive marker protein of the cell line in which it acts as an intracellular transglutaminase with roles in various intracytoplasmatic and intranuclear processes.…”