Expression Of Haptoglobin In Human Skin Cells

IntroductionNormal human epidermis is mainly composed of keratinocytes ( KC) , Langerhans cells ( LC ) , melanocytes, indeterminate dendritic cells, Merkel cells and lymphocytes.KC are the principal cells of the epidermis and constitute about 95% of all epidermal cells. KC play an important role in the protecting function of the skin. KC can produce keratins and mucopolysaccharides to keep skin integrity. KC is also an important constituent of the skin immune system ( SIS). Research works from 1980' s have revealed that KC can produce many kinds of cytokines to regulate the functions of LC and T cells in the skin. The molecules that KC can secrete include: interleukins (ILs) : IL-1a, IL-1β, IL-6, IL-8; interferons (IFNs);IFNa, IFNβ; colony stimulating factors (CSFs) : IL-3, GM -CSF, G - CSF, M - CSF; tumor necrosis factor a(TNFa); transforming growth factors (TGFs): TGFa, TGFβ and various other cytokines. So, KC could play an important role in the skin immunological reactions.Langerhans cells (LC) play a critical role in cutaneous immunological reactions for their antigen presenting properties even though LC constitute only 2% -5% of all epidermal cells. LC can take up and process the antigens coming into the epidermis from outside and present them to the T cells in the regional lymph nodes. LC is thought to subserve a critical role in cutaneous immuno -surveillance by virtue of their antigen - presenting capacity. But LC are functionally labile because they are easily affected by the factors around them. Freshly obtained (or intraepidermal) LC can readily activate allogeneic T cells, but they are incapable of activating autologous naive T cells. When the freshly separated LC are cultured for 2 - 3 days in the presence of KC, LC swiftly up -regulate surface expression of MHC class I and II molecules, and begin to ex-press de novo the products of numerous genes that encode molecules associated with co - stimulation of naive T cells: B7, ICAM-1, CD40 and IL-1b. In the same time, cultured LC acquire the novel functional property of activating autologous T cells. It is believed that KC - derived GM - CSF is the primary driving force responsible for the conversion of LC from immature to mature in vitro. But it is paradoxical that intracutaneous administration of exogenous GM -CSF fails to induce intraepidermal LC to undergo functional transformation in situ. Xie et al believe that there should be a factor in the serum that could prevent fresh LC from undergoing functional transformation in culture. They identified the factor as haptoglobin (Hp) (a1 chain). They also found that Hp was present normally in cytoplasm of intraepidermal or freshly obtained LC, and, after having been cultured 3 days in Hp free medium, most LC lost their Hp. They suggested that Hp in LC may not be synthesized by LC themselves. Hp is a kind of a2 - sialoglycoprotein, present in most body fluids of human and other mammals. Hp is a positive acute -phase reactant, and its plasma level is increased in inflammation, infection of different aetiology ,. trauma, tissue damage and malignant proliferation, but decreased in hemolytic conditions and in severe hepato-cellular deficiency. It has been reported that biosynthesis of Hp occurs not only in the liver, but also in adipose tissue, lung and other organs. But there is no data shown on the Hp mRNA expression in normal human skin ( neither epidermis nor dermis). DArmiento et al found that there was Hp mRN A expression in mouse skin, but did not indicate whether in the epidermis or in the dermis. To investigate whether normal human skin, especially the epidermal cells, can produce Hp, we did the following studies:1. Detected the Hp mRNA expression in 14 cases of normal human epidermis and dermis, using RT - PCR method;2. Detected the Hp mRNA expression in the epidermal cells prepared from 8 cases of normal human epidermis using in situ hybridization (ISH) method;3. Detected the Hp mRNA expression in a human KC cell line-HaCaTcells, using both RT -PCR and ISH me...