Sadao Imamura

FRACTALKINE AND MACROPHAGE-DERIVED CHEMOKINE : T CELL-ATTRACTING CHEMOKINES EXPRESSED IN T CELL AREA DENDRITIC CELLS

Dendritic cells (DC) are a system of antigen‐presenting cells specialized in interaction with T cells. Recently it has been reported that DC can produce CC (β) chemokines that attract T cells. In this study we isolated mouse fractalkine and macrophage‐derived chemokine (MDC) belonging to CX3C (δ) and CC chemokine families, respectively, from bone marrow‐derived mature DC. While expression of fractalkine, which has so far been only examined in the brain and in vitro endothelial cells so far, was rather ubiquitous, MDC, which has been reported to be synthesized by macrophages and DC, was expressed specifically in the thymus and lymphnode. This is the first report that indicates fractalkine expression by DC. Expression of fractalkine and MDC mRNA increased with maturation of DC during in vitro culture of bone marrow cells. Spleen‐ and epidermis‐derived mature DC in culture also expressed these chemokines. Furthermore, their expression was detected selectively by Northern hybridization in CD11c+ B220– DC freshly purified from lymph nodes, and in large stellate cells in the lymph node T cell areas by in situ hybridization. Conditioned media of 293T cells transfected with these chemokine cDNA were chemotactic to Con A‐activated splenic T cells as well as the mouse T cell line EL4. In conclusion, while fractalkine and MDC belong to different families of chemokines, both may be involved in recruitment of T cells for interaction with mature DC in the immune response.

The incidence of internal malignancies in pemphigus and bullous pemphigoid in Japan

To evaluate the significance of the association of malignancy with autoimmune blistering diseases, we studied the incidence of internal malignancies in pemphigus and bullous pemphigoid based upon 496 cases of pemphigus and 1113 cases of bullous pemphigoid in Japan. Results showed that (1) an association between internal malignancies and pemphigus was observed in 25 out of 496 cases (5.0%), while that with bullous pemphigoid was seen in 64 out of 1113 cases (5.8%). Such association ratios were significantly higher than that of the controls aged over 70 years old (0.61%); (2) The average ages of pemphigus/bullous pemphigoid with malignancy were 64.7 and 69.2 years, respectively. The association ratio of malignancy with pemphigus increased by age, while that with pemphigoid was not correlated with aging; (3) Lung cancer was most common in pemphigus and gastric cancer in bullous pemphigoid; (4) There were no significant differences in the titers of circulating antibody, the presence or extent of mucous involvement or annular erythema between bullous pemphigoid patients with malignancy and without malignancy. Our results indicated that detailed examination for internal malignancy is essential for those patients with pemphigus or bullous pemphigoid.

Monocyte-derived dendritic cells have a phenotype comparable to that of dermal dendritic cells and display ultrastructural granules distinct from Birbeck granules.

Most monocyte‐derived dendritic cells (DC) display CD1a, like Langerhans cells (LC) and some dermal DC, but their relationship with these skin DC remains unclear. To address this issue, we studied the expression of different antigens characteristic of skin DC and of monocyte/macrophages in CD1a+ and CD1a– monocyte‐derived DC. Their phenotype indicated that they may be related to dermal DC rather than to LC, i.e., they were all CD11b‐positive, and 72% were Factor XIIIa‐positive, but they did not express E‐cadherin nor VLA‐6. It is interesting that CD1a+ and CD1a– cells showed intracytoplasmic granules that were different from LC Birbeck granules. These pheno‐typical and ultrastructural features are comparable to those of CD14‐derived DC obtained from cord blood precursors [C. Caux et al. J. Exp. Med. 184, 695–706]. These results show a close relationship between these two in vitro models, which are both related to dermal DC. J. Leukoc. Biol. 64: 484–493; 1998.

Roles of E- and P-cadherin in the human skin.

The Ca2+‐dependent cell‐cell adhesion molecules, termed cadherins, are subdivided into several subclasses. E (epithelial)‐ and P (placental)‐cadherins are involved in the selective adhesion of epidermal cells.

Sunburn cell formation is prevented by scavenging oxygen intermediates

Effects of superoxide dismutase (SOD) (100–3000 U/ml), catalase (300–3000 U/ml), xanthine (1–10 mM/ml) and D‐mannitol (30–300 mM ml) were examined in the pathogenesis of sunburn cells. These agents were considered to quench oxygen intermediates. The skin specimens from clipped trunk of female ICR mice were irradiated in vitro with UV‐B (6o‐120 mJ/cm2). and then incubated for 24 h. The scavengers were added during both UV irradiation and incubation. In one of the SOD groups, SOD was added only during the UV irradiation.

Treatment of Acute Febrile Neutrophilic Dermatosis (Sweet’s Syndrome) with Potassium Iodide

6 cases with acute febrile neutrophilic dermatosis (Sweets syndrome) responded rapidly and dramatically to treatment with potassium iodide. All patients became afebrile and symptom-free within 24--48 h after therapy. The cutaneous eruptions subsided completely in 3--5 days. 5 of the patients received the drug only for 2 weeks, but they have had no recurrences. Although the remaining 1 patient had shown minor recurrences after cessation of the medication, he was free of all symptoms during the therapy. The mode of the action of potassium iodide is also discussed.

Regression of plane warts following spontaneous inflammation. An histopathological study.

This paper describes the clinical and histopathological features in ten cases of spontaneously involuting plane warts. In all, rapid regression occurred after the sudden development of an inflammatory reaction. At an early stage a degenerative change appears in the upper epidermis and the typic features of the warts are masked. At the height of the reaction an intense mononuclear cell infiltrate in the dermis associated with epidermal spongiosis, exocytosis cell necrosis and focal parakeratosis is found. It is suggested that the development of cell mediated immunity may be responsible for spontaneous involution of warts.

Erythema multiforme: demonstration of immune complexes in the sera and skin lesions

In twenty patients with erythema multiforme we investigated circulating immune complexes and their deposition in the skin lesions. C1q‐binding activity was elevated in ten of twenty patients, and the platelet aggregation titre was high in three of twelve tested sera. Decreased levels of C3 were seen in two and of C4 in one out of eighteen patients. Direct immunofluorescence showed a deposition of C3, IgM or IgG in the blood vessel walls of the upper dermis in four of twelve patients. These findings may suggest that transient production of circulating immune complexes and their deposition play an important role in the pathogenesis of this disease.

Anti‐oxidant action of metronidazole: a possible mechanism of action in rosacea

To elucidate the mechanism of action of metronidazole in the treatment of rosacea, the effect of metronidazole on the generation of reactive oxygen species was examined both in neutrophil and xanthine‐xanthine oxidase systems. Metronidazole had anti‐oxidant action which was not exerted by the scavenging of reactive oxygen species, but by having an effect on neutrophil cell functions. Beneficial effects of metronidazole in the treatment of papulopustular rosacea can in part be attributable to this anti‐inflammatory effect.

Potassium iodide in erythema nodosum and other erythematous dermatoses

Potassium iodide therapy has a history of more than 150 years. It has been tried in many diseases in the past. However, with the development of modern medications indications for potassium iodide therapy are very limited. It is well known that potassium iodide is the drug of choice for sporotrichosis. Subacute nodular migratory panniculitis and erythema nodosum have also been treated successfully with this drug.