Lesional T cells and dermal dendrocytes in psoriasis plaque express increased levels of granulysin

Stanford University, Palo Alto, California, United States
Journal of the American Academy of Dermatology (Impact Factor: 5). 01/2005; 51(6):1006-8. DOI: 10.1016/j.jaad.2003.10.679
Source: PubMed

ABSTRACT Granulysin is a broad-spectrum potent antimicrobial peptide produced by the immunocytes. We determined granulysin levels in certain cutaneous inflammatory diseases and correlated expression of granulysin with the relative risks of secondary infections in these conditions. In immunohistochemistry stains a monoclonal antigranulysin antibody was used at 1:150 dilutions. Compared with atopic dermatitis and nummular eczema lesions where secondary infection with Staphylococcus aureus is very common, we found that a significantly increased number of granulysin-positive T cells (P < .01) were present in psoriatic plaques. Psoriasis plaques are heavily colonized with S aureus . It is a well-known observation that despite open cracks and fissures these plaques do not get infected. Increased levels of granulysin provide an explanation for relative immunity of psoriatic plaques against both gram-positive and gram-negative bacterial infections.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Packet reordering has been shown to be an ever-increasing phenomenon on the Internet and must be taken into account when considering performance analysis of both fixed, wireless and mixed media networks. Previous work (J. Bennet et al., 1999) has demonstrated that TCP suffers degraded performance in situations of high packet reordering. This paper will consider why video traffic over UDP also performs badly in situations of high packet reordering, due to the temporal inter-packet dependencies introduced by the MPEG video encoding structure. Wireless networks are especially prone to problems due to the higher levels of link layer retransmissions found in noisy wireless environments. An experimental investigation into the effects of video packet reordering using the Windows Media streaming system is presented. A method for invoking packet reordering is introduced, and a tool for client-side measurements of video quality is presented. Typical measurements of video performance undergoing reordering are shown, with a study of buffering occupancy at the client, and the potential impact this could have on video packet reordering demonstrated.
    Wireless Communication Systems, 2004, 1st International Symposium on; 10/2004
  • [Show abstract] [Hide abstract]
    ABSTRACT: The recent global increase in cases of tuberculosis and the emergence of multidrug-resistant strains of tuberculosis have focused attention on the molecular mechanisms of human antimycobacterial immunity. The macrophage is not only the primary site for Mycobacterium tuberculosis growth but also ordinarily provides the primary lines of host defense against invading pathogens in its role as an effector of innate immunity. The ability of M. tuberculosis to survive and replicate in the host macrophage is critical to its pathogenesis, emphasizing a need for a clearer understanding of its interactions with the host macrophage. Macrophages use varied strategies to kill and destroy invading organisms, including production of reactive nitrogen and oxygen intermediates, phagosome maturation and acidification, fusion with lysosomes, exposure to defensins and host cell apoptosis. In human, granulysin is a recently identified antimicrobial protein expressed on cytotoxic T cells, natural killer (NK) cells and NKT cells. It has been shown that granulysin contributes to the defense mechanisms against mycobacterial infection. We hypothesized that human macrophages may possess antimicrobial substances, such as granulysin, and play a role in the defense mechanism.
    Pathologie Biologie 10/2005; 53(8):516-521. DOI:10.1016/j.patbio.2005.07.003
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The understanding of the pathogenesis of psoriasis vulgaris has focused on T cell mediated immune disorder for many years. Recent studies provide evidence that dendritic cells may be of major importance as regulatory cells driving the psoriasis tissue reaction, and they are one of the therapeutic targets. In order to further characterize the role of dendritic cells in psoriasis, this study was designed to assess the differentiation of dendritic cells from monocytes (MoDC), the expression of phagocytosis related receptors by MoDC, their endocytic activity for fluorescent beads and lucifer yellow as well as their superoxide generation in patients with psoriasis. Twenty eight patients with psoriasis vulgaris and 12 healthy controls were included in the study. MoDC were obtained by culturing monocytes with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 5 days. Cell surface expression of CD1a, CD14, CD40, CD80, CD83, CD86, HLA-DR, mannose receptor (MR) and Fcg receptors by MoDC and their endocytosis of dextran and lucifer yellow were analyzed by flow cytometry. Zymosan ingestion was measured to access the phagocytosis of MoDC. Differentiation of monocytes to dendritic cells was upregulated in patients manifested as significantly increased expression of CD40, CD80, CD86 and HLA-DR compared with that in healthy controls (P<0.01). Expression of MR and Fcg receptor II (CD32) by MoDC was significantly increased in patients with psoriasis as well (P<0.01). Endocytosis of dextran but not lucifer yellow in patients was significantly higher than controls (P<0.01), and significantly enhanced phagocytosis by increasing zymosan ingestion was also observed (P<0.01) in patients. Taken together, endocytic and phagocytic activity of MoDC in psoriasis was increased than normal persons. Enhanced activity of dendritic cells binding and capturing foreign antigens for subsequent antigen presentation and the initiation of immune responses in psoriasis may contribute to the pathogenesis of the disease. The upregulated expression of MR and the enhanced endocytic activity of DC might be an explanation for the absence of skin infection observed in psoriasis.
    The Indian Journal of Medical Research 01/2006; 123(1):43-50.

Similar Publications