Masaharu Matsukura

RANTES mRNA Expression in Skin and Colon of Patients with Atopic Dermatitis

The expression of RANTES mRNA in dermal and colonic tissue was examined in patients with atopic dermatitis by the reverse transcription polymerase chain reaction method. RANTES mRNA was detected in the colon in 8 of 10 patients and in 1 of 5 control patients. It was present in rashes in 9 of 10 patients and at non-eruptive sites in 5 of 7 patients. These findings suggest that RANTES is involved in eosinophil infiltration and T cell infiltration in atopic dermatitis.

Enhanced production of RANTES, an eosinophil chemoattractant factor, by cytokine-stimulated epidermal keratinocytes.

In allergic skin diseases such as atopic dermatitis (AD), eosinophils migrate from the circulation to the skin. We investigated the mechanisms of eosinophil chemotaxis in atopic dermatitis by examining the effect of stimulation of epidermal keratinocytes (KC) by inflammatory cytokines, interferon-gamma (IFNgamma) and/or tumor necrosis factor-alpha (TNF alpha) on the production of eosinophil chemotactic factors. Simultaneous addition of IFNgamma and TNF alpha to culture KC synergistically increased eosinophil chemotaxis and the expression of RANTES mRNA and protein level on these cells. Anti-RANTES antibody blocked eosinophil chemotaxis by IFNgamma- and TNF alpha-stimulated KC. Our results indicate that the production of RANTES by KC may help to explain eosinophil infiltration into the skin in AD.

Epinastine Inhibits Eosinophil Chemotaxis and Adhesion Molecules in Atopic Dermatitis

Purpose: To investigate the effects of epinastine on eosinophil chemotaxis and changes in eosinophil adhesion molecules induced by epinastine and three other antiallergic agents, using eosinophils of atopic dermatitis (AD) patients. Results: Epinastine reduced eosinophil chemotaxis toward eotaxin when the eosinophils had been prestimulated with interleukin (IL)-5, but given alone it did not alter eosinophil chemotaxis toward IL-5. CD11b expression was inhibited when peripheral blood was prestimulated with IL-5, but eosinophil adhesion molecule expression was not altered. Conclusions: Epinastine suppresses allergic inflammation not only through its strong antihistamine and antimediator effects, but also by inhibiting eosinophilic chemotaxis and the expression of adhesion molecules involved in chemotaxis, especially CD11b.

Overexpression of CD11b on Eosinophils in Atopic Dermatitis: Downregulation by Cyclosporin A and Upregulation by Interleukin 5

We examined the level of expression of CD11b on eosinophils in pripheral blood samples from patients with atopic dermatitis (AD) and non-AD volunteers. Eosinophils were defined using a new method employing CD14/CD45 and a backgate technique. Overexpression of CD11b was noted in eosinophils of AD patients. Treatment of AD with cyclosporin A resulted in clinical improvement as well as reduction in the expression of CD11b. Stimulation of eosinophils from patients with inactive AD by interleukin 5 upregulated the expression of CD11b on these cells. Our results suggest that the expression of CD11b surface molecule on eosinophils may play an important role in the activity of AD.

Immunohistology of skin and oral biopsies in graft-versus-host disease after bone marrow transplantation and cytokine therapy

BACKGROUND Early diagnosis of graft-versus-host-disease (GVHD) after bone marrow transplantation is often difficult, particularly when the patients are immunosuppressed by chemotherapy or irradiation. OBJECTIVE To investigate the influence of cytokines on skin lesions after bone marrow transplantation. METHODS Biopsy specimens of skin and oral mucosa were obtained from bone marrow transplant patients with GVHD and were subjected to histologic and immunohistochemical examination. RESULTS Administration of granulocyte-macrophage colony-stimulating factor caused atopic dermatitis-like lesions in two patients, who had infiltration of neutrophils, eosinophils, and lymphocytes around the hair follicles of the skin and no signs of GVHD in other organs. Only patients who were treated with cytokines developed acute GVHD. Immunohistochemical examination of skin biopsies from 18 patients with acute GVHD and 11 patients with chronic GVHD after cyclophosphamide administration or irradiation showed that the maculopapular skin lesions characteristic of acute GVHD contained infiltrates of CD4+ and CD8+ lymphocytes. There was also an increase in numbers of epidermal keratinocytes expressing intercellular adhesion molecule-I and HLA-DR antigens. CONCLUSION These findings support the involvement of cytokines in GVHD and suggest that immunostaining of skin biopsies may be useful for the early diagnosis of this condition.

Steroid-Induced Changes of Eosinophils in Atopic Dermatitis

We investigated whether apoptosis of eosinophils is specific to atopic dermatitis (AD), or also occurs in other diseases with eosinophilia. We examined the survival of eosinophils cultured with corticosteroids: (1) Clinically, steroid administration significantly decreased high peripheral blood eosinophil cell counts in patients with AD. (2) Treatment with recombinant human (rh) IL-5 prolonged the life span of eosinophils derived from patients with AD and of those derived from non-AD patients with eosinophilia. However, there were differences in the survival rates in the presence of rhIL-5: the eosinophils from non-AD patients showed 1.4-fold higher survival rates than those from AD patients at 24 h. In the presence of steroids, the eosinophils from non-AD patients showed a survival rate double that of those from AD patients at 24 h. (3) In eosinophils from patients with AD, the survival rate decreased significantly in a time- and steroid-concentration-dependent manner. Steroid administration significantly inhibited the survival rate of eosinophils from patients with AD compared to those of monocytes and neutrophils. These findings suggest that apoptosis induced by steroids decreases the eosinophil count in vivo in patients with AD. There may be a difference in the incidence of steroid-induced apoptosis between eosinophil cells from patients with AD and those from patients with eosinophilia due to other underlying diseases.