The CD48 receptor mediates Staphylococcus aureus human and murine eosinophil activation.

BACKGROUND: Allergy is characterized by eosinophilia and an increased susceptibility to microbial infection. Atopic dermatitis (AD) is typically associated with Staphylococcus aureus (SA) colonization. Some of the mechanisms by which SA and its exotoxins interact with eosinophils remain elusive. CD48, a glycosylphosphatidylinositol-anchored receptor belonging to the CD2 family, participates in mast cells-SA stimulating cross-talk, facilitates the formation of the mast cell/eosinophils effector unit and as expressed by eosinophils, mediates experimental asthma. OBJECTIVE: To investigate the role of CD48 expressed on human peripheral blood and mouse bone marrow-derived eosinophils (BMEos) in their interaction with heat-killed SA and its three exotoxins, Staphylococcal enterotoxin B (SEB), protein A (PtA) and peptidoglycan (PGN). METHODS: Eosinophils were obtained from human peripheral blood and BM of WT and CD48-/- mice. SA was heat killed and eosinophils-SA/exotoxins interactions were analyzed by confocal microscopy, adhesion and degranulation, cell viability, cytokine release and cell signalling. In addition, peritonitis was induced by SEB injection into CD48-/- and WT mice. CD48 expression was studied in AD patients' skin and as expressed on their leucocytes in the peripheral blood. RESULTS: We provide evidence for the recognition and direct physical interaction between eosinophils and SA/exotoxins. Skin of AD patients showed a striking increase of eosinophil-associated CD48 expression while on peripheral blood leucocytes it was down-regulated. SA/exotoxins enhanced CD48 eosinophil expression, bound to CD48 and caused eosinophil activation and signal transduction. These effects were significantly decreased by blocking CD48 on human eosinophils or in BMEos from CD48-/- mice. We have also explored the role of CD48 in a SEB-induced peritonitis model in CD48-/- mice by evaluating inflammatory peritoneal cells, eosinophil numbers and activation. CONCLUSIONS: These data demonstrate the important role of CD48 in SA/exotoxins-eosinophil activating interactions that can take place during allergic responses and indicate CD48 as a novel therapeutic target for allergy and especially of AD.

Well being, psychopathology and coping strategies in psoriasis compared with atopic dermatitis: a controlled study.

BACKGROUND: There is a vast literature describing the association between psoriasis, atopic dermatitis (AD) and psychological distress. Some of these studies were uncontrolled and others used non-dermatological diseases as control, but only a few used chronic skin diseases as controls. OBJECTIVE: To compare well being, psychopathology and coping strategies of psoriatic, AD and healthy controls in a prospective case-control study. METHODS: Thirty-seven psoriatic patients and 31 AD patients were recruited from the Hadassah Ein Karem Hospital, Jerusalem, Israel, outpatient and inward clinic. The participants in the control group were 31 healthy workers and volunteers with no dermatological diseases from Kaplan Hospital, Rehovot, Israel. We used self-report questionnaires [Mental Health Inventory (MHI) and Adjustment to Chronic Skin Diseases Questionnaire (ACSD)], a projective technique (Hand Test) and assessment tools (Clinical Global Impression). RESULTS: Psoriatic patients experienced reduced well being (P = 0.007) and more anxiety and depression (P = 0.018) than normal controls. Psoriatic patients also displayed more severe psychopathology (P = 0.039) a more passive attitude towards life, and loss of meaning in life (P = 0.001) as measured by the projective technique compared with AD patients and normal controls. CONCLUSIONS: We propose two explanations, derived from the psychological and the psycho-neuro-immunological domains. First, greater mental distress in psoriasis is because of the greater stigma it bears compared with AD. Alternatively, we hypothesize that the psoriatic inflammatory process may possibly have a direct central nervous system effect.

Immunological assessment of familial tinea corporis.

BACKGROUND: The mechanisms involved in the immune resistance to fungal infection of the skin are not well understood. We assessed the levels of the various lymphocyte subsets, the HLA haplotypes, the expression of various receptors on natural killer (NK) cells and the serum levels of cytokines, in a family in which four siblings had tinea corporis, while four others were healthy, in order to reveal potential factors of susceptibility to dermatophytes. OBSERVATIONS: Normal numbers of T, B and NK cells were found in the peripheral blood, without significant differences between healthy and infected siblings. The frequency of CD14-positive monocytes was elevated in infected compared with healthy siblings. The proportion of NKG2A(+) NK cells was reduced in the patients compared with healthy siblings (23.8% vs. 33.8%), whereas CXCR3(+) NK cells were increased (41.5% vs. 25.6%, respectively). MHC class I and class II haplotypes were disease independent. Elevated levels of intereron-gamma, interleukin-8 (IL-8), IL-2 and tumour necrosis factor-alpha (TNFalpha) were observed only in part of the infected siblings. The serum level of TNFalpha was strongly correlated with the percentage of CD14(+) monocytes. CONCLUSIONS: We studied here in detail the NK functions of a family of patients suffering from tinea corporis and observed skewed frequencies of specific NK receptors, which imply possible involvement of NK cells in susceptibility to fungal infection.

Acro-angiodermatitis: review of the literature and report of a case.

Acro-angiodermatitis is a very common disorder, with a close clinical, anatomical and morphological resemblance to Kaposi's sarcoma. Several types of this disorder can be found in different settings. However, these conditions are often misdiagnosed and therefore mistreated. A review of the literature and a classification of all types of acro-angiodermatitis are presented. We also describe a case of a patient with acro-angiodermatitis which completely regressed following a course of dapsone combined with leg elevation and elastic support stockings.

Imbalance of immune responses in patients with chronic and widespread fungal skin infection.

Fungal infections of the skin are caused by dermatophyte fungi. Infections can be acute and inflammatory or chronic and non-inflammatory; it is believed that cell-mediated immunity is the cornerstone of host defence and is instrumental in the eradication of the infection. We describe here parameters of the immune response of a group of patients who although not immunocompromised, suffered from widespread and chronic infections. All patients lacked a specific delayed-type hypersensitivity (DTH) response; however, their in vitro lymphocyte proliferation in response to Trichophyton rubrum extract and to other fungal antigens was normal. The patients were not atopic by clinical history, and yet had high levels of non-specific IgE and of T. rubrum-specific IgG4. Taken together, the results of this study suggest that the group of patients studied suffered from an immune imbalance which has characteristics of a Th2-type response.

Unusually extensive disease caused by Leishmania major parasites.

Simple cutaneous leishmaniasis (CL), which is endemic in several areas of Israel, is usually caused by Leishmania major. CL, which is caused by replication of parasites within dermal macrophages, is self-limited and almost always confined to the skin. We recently encountered two cases of CL in which skin defenses were breached and lesions appeared in subcutaneous locations. In one case, abnormal cell-mediated immune function was detected. The purpose of this article is to present these data and to comment on the immunological aspects of leishmaniasis.

Leishmania major and Leishmania donovani: effect of LPG-containing and LPG-deficient strains on monocyte chemotaxis and chemiluminescence.

Lipophosphoglycan (LPG) is a major glycolipid present on the membrane of Leishmania promastigotes and amastigotes. We have previously shown that preincubation of peripheral blood monocytes with purified LPG inhibits IL-1 production, chemotactic locomotion, and luminol-dependent chemiluminescence (LDCL). In the present study we tested the effect of LPG present on live parasites on monocyte activity. For this purpose, we used two mutant strains deficient in LPG and two LPG-containing strains. One pair was Leishmania major and the other Leishmania donovani. Monocytes in suspension were infected with the different parasite strains and tested for chemotactic locomotion and LDCL at different times between 1 and 72 hr after infection. In parallel, the percentage of infected monocytes was measured in stained cytospin preparations. The results obtained showed that at 1 hr of incubation only the LPG-containing strains inhibited chemotaxis, while the mutant strains showed a normal response. From 4 hr of incubation onwards, the mutant strains also inhibited monocyte chemotactic locomotion. LDCL was only slightly inhibited by the LPG-containing strains after 1 hr, because of a high level of spontaneous stimulation, probably due to phagocytosis. At 24 and 72 hr all strains inhibited LDCL. These results suggest that LPG is responsible for early inhibition of macrophage activity, but that other factors are responsible for inhibition at later stages of in vitro infection. The model described here might represent a useful tool to further analyze the mechanisms involved in immune evasion of Leishmania parasites.

Superficial actinic porokeratosis and cystic fibrosis.

A 24-year-old woman, presenting with cystic fibrosis, developed superficial actinic porokeratosis. Immunosuppression due to cystic fibrosis may be either the cause of or the exacerbating factor in superficial actinic porokeratosis in our patient.

Effect of glycolipids of Leishmania parasites on human monocyte activity. Inhibition by lipophosphoglycan.

Lipophosphoglycan (LPG) and glycosyl phosphatidylinositol Ag (GPI), are glycolipids present on the membrane of Leishmania parasites. Both glycolipids have been chemically characterized. LPG is a polysaccharide of repeating phosphorylated units linked to a phosphocarbohydrate core that is anchored to the membrane by lysoalkyl phosphatidylinositol (PI). The GPI are smaller glycolipids with a structure resembling the phosphocarbohydrate core of the LPG. They are anchored to the membrane by alkyl acyl PI. Their relative abundance, uniqueness of structure, and cellular location suggest a role in interactions of the parasites with host cells. In the present study we examined the effect of LPG and GPI on the activation of human peripheral blood monocytes. Three parameters were studied: the production of IL-1, chemotactic locomotion, and oxidative burst. We found that whereas neither GPI nor LPG directly affected monocyte activity, preincubation of the monocytes with LPG strongly inhibited further activation: The production of IL-1, after stimulation with LPS, was decreased in a dose-dependent manner. Previous incubation with LPG also inhibited chemotactic locomotion of monocytes and neutrophils in response to diacylglycerol, zymosan-activated serum, FMLP and LTB4. Luminol-dependent chemiluminiscence caused by stimulation of the monocytes with streptococci and histone was also inhibited. After fragmentation of the LPG into phosphoglycan and 1-O-alkylglycerol by phosphatidylinositol-phospholipase C, only the phosphoglycan retained inhibitory activity. No difference in inhibitory activity was found between LPG prepared from Leishmania major or Leishmania donovani promastigotes. These results show that the phosphoglycan of LPG inhibits the immunologic response of normal human monocytes and neutrophils, and suggest that LPG may influence the nature of the inflammatory response surrounding infected cells.

Effect of zinc therapy on neutrophil chemotaxis in psoriasis.

Neutrophil chemotaxis in patients with psoriasis vulgaris and psoriatic arthritis was investigated before and after 6 weeks of treatment with zinc sulphate (50 mg elementary zinc three times daily). In patients with active psoriasis vulgaris, a significant increase in neutrophil random migration and directed chemotaxis was demonstrated (10.2 +/- 3.1 and 14.1 +/- 4.1 mu, respectively, greater than that of control patients), while in patients with psoriatic arthritis the values were within the normal range (5.8 +/- 3.2 and 1.1 +/- 4.1 mu, respectively, greater than that of control patients). Although the zinc sulphate treatment had little or no effect on the course of either disease, it restored both the random migration and directed chemotaxis to normal values in psoriasis vulgaris patients. These results support the contention that zinc sulphate modifies neutrophil inflammatory potential; however, the lack of a clinical benefit suggests that neutrophils play only a secondary role in the pathogenesis of psoriasis.

An oral zinc loading test in psoriasis.

Changes of zinc in body fluids were evaluated in 12 patients with extensive psoriasis and compared with those of 11 healthy volunteers, using an oral zinc loading test. Plasma zinc levels and urinary zinc excretion were measured by atomic absorption spectrophotometry. No significant difference was found between plasma zinc levels and urinary zinc excretion following an overnight fast. Both groups showed extensive increases in urinary zinc excretion following the loading test. The peak levels of plasma zinc were significantly lower in the psoriatic patients two and four hours after zinc ingestion (P less than .01 and P less than .02, respectively).

Treatment with itraconazole of widespread tinea corporis due to Trichophyton rubrum in a bone marrow transplant recipient.

An immunocompromised patient, 6 weeks after bone marrow transplantation, developed extensive skin infection due to Trichophyton rubrum. Because she could not tolerate ketoconazole and was hypersensitive to griseofulvin, she received itraconazole with complete recovery within 30 days. This case demonstrates that itraconazole may be effective treatment for dermatophytosis, even in immunocompromised hosts, and that there is no cross-reactivity between ketoconazole and itraconazole.

Generalized morphea and idiopathic thrombocytopenia.

A patient with generalized morphea and thrombocytopenia is reported. The thrombocytopenia responded promptly to corticosteroid and immunosuppressive therapy but recurred when the steroids were discontinued. The occurrence of thrombocytopenia in generalized morphea suggests a common immune mechanism and emphasizes the need to look for concomitant autoimmune hematologic disorders in patients with systemic, as well as localized, scleroderma.

Polymorphous drug eruption due to nifedipine.

A patient who underwent coronary bypass surgery and was treated with nifedipine subsequently developed an erysipelaslike erythematous itching plaque on both shins. Histopathologic examination of a biopsy specimen from the area showed findings compatible with a lichen-planus-like drug eruption. An awareness of varied skin reactions produced by nifedipine may reduce the suffering of patients and help prevent unnecessary local and general treatments.