Expression of cutaneous lymphocyte-associated antigen (CLA) in tonsillar T-cells and its induction by in vitro stimulation with alpha-streptococci in patients with pustulosis palmaris et plantaris (PPP)

Academic Press, Nozawa, Hayabusa ; Kishibe, Kan ; Takahara, Miki ; Harabuchi, Yasuaki, Clinical Immunology, 116(1), 2005, 42-53. authorPustulosis palmaris et plantaris (PPP) is known to be a one of the tonsil-related diseases because tonsillectomy is quite effective in curing this condition. However etiological association between tonsils and PPP have not fully clarified yet. Cutaneous lymphocyte-associated antigen (CLA) is known to be a specific homing receptor that facilitates T-cell migration into skin. In this study, we investigated the expression of CLA on T-cells in tonsil, peripheral blood, and skin from patients with PPP. Two-color flow cytometric and two-color immunohistological analyses revealed that the numbers of CLA/CD3 double-positive cells in freshly isolated tonsillar mononuclear cells (TMC) and in tonsillar tissues were significantly higher in patients with PPP than in patients without PPP (P < 0.01, each). In vitro stimulus with α-streptococcal antigens enhanced CLA expression of tonsillar T-cells and TGF-β production of TMC in patients with PPP (P < 0.01, each), but did not in patients without PPP. In peripheral blood from PPP patients, the number of the CLA/CD3 double-positive cells significantly decreased at 6 months after tonsillectomy (P < 0.05). The CLA/CD3 double-positive cells and the postcapillary venule that expressed with a ligand of CLA, E-selectin, were found more frequently in the plantar skin from patients with PPP as compared to that from healthy volunteers (P < 0.01, each). These data suggest that a novel immune response to α-streptococci may enhance CLA expression on tonsillar T-cells through TGF-β production in patients with PPP, resulting in moving of CLA-positive tonsillar T-cells to skin and tissue damages. This may play a key role in pathogenesis of PPP

Rab11 Is Associated with Epidermal Lamellar Granules

Nature Publishing Group, Journal of Investigative Dermatology, 127, 9, 2007, 2166-2170 authorEpidermal lamellar granules (LGs) are specialized organelles that transport and secrete various molecules, including lipids, proteases, protease inhibitors, and structural proteins, thereby providing a protective barrier against the environment. Abnormalities in LG-related molecules result in severe skin diseases, but their transport mechanisms are poorly understood. We studied the distribution of Rab11, a common GTPase in recycling endosomes, in normal human epidermis. Confocal laser scanning microscopy detected Rab11 immunoreactivity in differentiated epidermal keratinocytes. Staining was strong at the apical side of each cell, a pattern commonly seen in LG-associated molecules. Around the nuclei, Rab11 was colocalized with TGN46, a trans-Golgi network marker. Rab11 was also colocalized with known LG-molecules, namely lymphoepithelial Kazal-type-related inhibitor, corneodesmosine, cathepsin D, and glucosylceramides. Immunoelectron microscopy revealed that Rab11 was widely distributed along TGN and tubular-vesicular structures containing different LG molecules. The present results suggest that Rab11 plays a role in the intracellular trafficking of various types of LG-molecule from the TGN to the cell surface

A study of costimulatory factors in tonsils of pustulosis palmaris et plantaris

Elsevier, Kan, Kishibe ; Miki, Takahara ; Hayabusa, Nozawa ; Yasuaki, Harabuchi, International Congress Series, 1257, 2003, 293-297. authorPustulosis palmaris et plantaris (PPP) is known to be closely related to tonsillar focal infections and tonsillectomy is quite effective. Hyper-immune response to alpha streptococci in patients with PPP was reported. On the other hand, costimulatory factors were studied on autoimmune disease. CD28 and cytotoxic T lymphocyte-associated 4 (CTLA4) participate in these factors. CD28 take part in T-cell activation, while CTLA4 take part in T-cell suppression. Therefore, we investigated CD28 and CTLA4 mRNA levels by reverse transcription-polymerase chain reaction (RT-PCR) in tonsillar tissues and CD3 positive lymphocytes from patients with PPP, recurrent tonsillitis (RT), and obstructive sleep apnea syndrome (OSAS). We also investigated the expression levels of CD28 and CTLA4 by flow cytometry analysis in tonsillar mononuclear cells stimulated with alpha streptococci in these patients. It was revealed that the CTLA4 mRNA in tonsillar CD3 positive lymphocytes from PPP patients was expressed at lower level than non-PPP patients. Then, the expression levels of CTLA4, comparison before and after stimulation, were lower level in PPP patients than non-PPP patients. These results suggest that the lower expression level of CTLA4 in PPP may cause hyper-immune response to alpha streptococci and abnormal regulation of T-cell activation

Lamellar granule secretion starts before the establishment of tight junction barrier for paracellular tracers in mammalian epidermis

PublisherDefects in epidermal barrier function and/or vesicular transport underlie severe skin diseases including ichthyosis and atopic dermatitis. Tight junctions (TJs) form a single layered network in simple epithelia. TJs are important for both barrier functions and vesicular transport. Epidermis is stratified epithelia and lamellar granules (LGs) are secreted from the stratum granulosum (SG) in a sequential manner. Previously, continuous TJs and paracellular permeability barriers were found in the second layer (SG2) of SG in mice, but their fate and correlation with LG secretion have been poorly understood. We studied epidermal TJ-related structures in humans and in mice and found occludin/ZO-1 immunoreactive multilayered networks spanning the first layer of SG (SG1) and SG2. Paracellular penetration tracer passed through some TJs in SG2, but not in SG1. LG secretion into the paracellular tracer positive spaces started below the level of TJs of SG1. Our study suggests that LG-secretion starts before the establishment of TJ barrier in the mammalian epidermis

Value of biological factors for prognosis in maxillary sinus squamous cell carcinoma: p53 gene mutation and apoptosis

Elsevier, Nobuyuki, Bandoh ; Tatsuya, Hayashi ; Kan, Kishibe ; Miki, Takahara ; Masanobu, Imada ; Satoshi, Nonaka ; Yasuaki, Harabuchi, International Congress Series, 1240, 2003, 489-490 autho

Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury

authorPrevious studies indicated that the expression of neuropsin, a serine protease, is induced in mature oligodendrocytes after injury to the central nervous system (CNS). The pathophysiology of spinal cord injury (SCI) involves primary and secondary mechanisms, the latter contributing further to permanent losses of function. To explore the role of neuropsin after SCI, histochemical and behavioral analyses were performed in wild-type (WT) and neuropsin-deficient (neuropsin^) mice using a crush injury model, a well-characterized and consistently reproducible model of SCI. In situ hybridization revealed that neuropsin mRNA expression was induced in the spinal cord white matter from WT mice after crush SCI, peaking at day 4. Neuropsin^ mice showed attenuated demyelination, oligodendrocyte death, and axonal damage after SCI. Although axonal degeneration in the corticospinal tract was obvious caudal to the lesion site in both strains of mice after SCI, the number of surviving nerve fibers caudal to the lesion was significantly larger in neuropsin^ mice than WT mice. Behavioral analysis revealed that the recovery at days 10-42 was significantly improved in neuropsin^ mice compared to WT mice in spite of the severe initial hindlimb impairments due to SCI in both strains. These observations suggest that neuropsin is involved in the secondary phase of the pathogenesis of SCI mediated by demyelination, oligodendrocyte death, and axonal degeneration