Elsevier

Clinical Immunology

Volume 131, Issue 3, June 2009, Pages 495-500
Clinical Immunology

Platelet-derived microparticles and soluble P-selectin as platelet activation markers in patients with atopic dermatitis

https://doi.org/10.1016/j.clim.2009.01.006Get rights and content

Abstract

Plasma levels of platelet-derived microparticles (PDMPs) and soluble P-selectin (sP-selectin) were investigated as markers of platelet activation in 46 atopic dermatitis (AD) patients, 20 non-atopic urticaria patients and 22 healthy controls. The relationships between these markers and the scoring AD (SCORAD) index, blood eosinophil number, serum IgE, and serum lactate dehydrogenase were also investigated in AD patients. Plasma PDMPs and sP-selectin levels were significantly higher in AD patients compared with the other two groups. In multiple regression analysis, the SCORAD index was the most significant factor associated with the platelet activation markers. Among the SCORAD index components, excoriations were most closely related to the markers. The elevated levels of PDMPs and sP-selectin were significantly reduced following skin lesion improvement by drug treatment. Our results show that blood platelets are activated in AD patients upon aggravation of eruption, suggesting that activated platelets may be involved in the pathomechanism of AD.

Introduction

It is increasingly widely understood that platelets have roles in inflammatory and immune processes, in addition to their function in hemostasis and thrombosis[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]. On activation by thrombin, collagen, adenosine diphosphate, chemokines and high shear stress, platelets rapidly release soluble immune mediators stored in α or dense granules, including chemokines, cytokines, and antibacterial proteins that induce and maintain inflammatory reactions [1], [2]. Platelets also migrate extravascularly and accumulate in inflammatory lesions concomitantly with leukocytes in response to a stimulation such as antigen exposure [3], [4], and have been associated with pathomechanisms of inflammatory disorders such as asthma[3], [4], [5], [6], [7], [8], [9], [10], [11], arthritis [12], [13] and inflammatory bowel disease [14], [15], [16].

Atopic dermatitis (AD) is a recurrent pruritic eczematous skin disease that is characterized by high serum IgE levels, increased levels of T helper 2-type cytokines such as interleukin (IL)-4, IL-5 and IL-13, positive immediate hypersensitivity to food or environmental allergens, and peripheral blood eosinophilia [17], [18]. In patients with AD, scratching due to severe itch often results in excoriation and subsequent platelet aggregation at the inflamed skin lesion, implying that blood platelets may be activated compared with those in normal individuals. We and others have shown that plasma levels of β-thromboglobulin and platelet factor 4, which are widely known as platelet activation markers, are significantly increased in patients with AD [19], [20], suggesting that platelets may be important in the pathomechanism of AD.

During platelet activation, microparticles are formed from the surface membrane of platelets by an exocytotic budding process [21]. These platelet-derived microparticles (PDMPs) range in size from 0.02 to 0.1 μm and have both pro- and anticoagulant activities[22]. PDMPs have been detected in blood from patients with activated coagulation and fibrinolysis [23] and autoimmune thrombocytopenia [24], [25], and also after cardiopulmonary bypass [26]. The adhesion molecule P-selectin is also expressed on activated platelets. This molecule is stored in the α-granules of platelets and in Weibel-Palade bodies of endothelial cells. Upon cell activation, P-selectin is expressed on the cell surface and secreted into plasma [27], [28]. Soluble P-selectin (sP-selectin) in plasma has been reported to originate from platelets [29]. Increased levels of sP-selectin are found in diseases such as thrombotic thrombocytopenic purpura [30], eclampsia [31], thromboembolic diseases [32], and diabetes [33]. Based on these findings, PDMPs and sP-selectin are regarded as platelet activation markers, but the plasma levels of these markers have not been determined in patients with AD.

In the current study, we evaluated platelet activity based on the plasma levels of PDMPs and sP-selectin in AD patients, non-atopic urticaria patients and healthy controls, and then investigated the relationship between the platelet activation markers and clinical parameters in AD. We also examined changes in the marker levels in association with improvement of eruption in AD.

Section snippets

Subjects

Forty-six adult patients (21 men, 25 women; median age: 28 years old; range: 17–52 years old) with AD were enrolled in the study. Diagnosis of AD was based on the criteria of Hanifin and Rajka [34] and clinical severity was determined using the scoring AD (SCORAD) index [35] (median score: 47.2; range: 24.5–59.8). The peripheral eosinophil count (median: 780; range: 300–1600/μl; reference range: 50–590/μl), serum IgE (median: 4150; range: 839–81200 IU/ml; reference range: 0–380 IU/ml), and

Plasma levels of PDMPs and sP-selectin in AD patients and non-atopic individuals

The plasma levels of PDMPs were significantly higher in AD patients (42.3 ± 6.2 U/ml) compared with those in non-atopic urticaria patients (20.7 ± 4.4 U/ml, P < 0.01) or control subjects (18.2 ± 2.5 U/ml, P < 0.01), and a similar significant elevation of plasma sP-selectin levels was found in AD patients (148.7 ± 10.1 U/ml) compared to urticaria patients (101.8 ± 9.5 U/ml, P < 0.01) and controls (98.7 ± 8.0 ng/ml, P < 0.01) (Fig. 1A). These data suggest that circulating platelets are activated in patients with AD

Discussion

The results of the study show for the first time that plasma levels of PDMPs and sP-selectin are both significantly elevated in AD patients compared with urticaria patients and healthy controls, suggesting that circulating platelets are activated in AD patients. The SCORAD index was significantly associated with the plasma levels of PDMPs and sP-selectin, and the elevated levels were significantly reduced after clinical improvement of skin lesions. We have also observed elevation of plasma

Acknowledgments

This study was supported by a grant from the Ministry of Education, Science, Sports, and Culture (to R.T.M. and N.K.), a grant for Basic Dermatological Research from Shiseido Co. Ltd. (to R.T.M.), and a grant from the Cosmetology Research Foundation (to N.K.).

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