Dermal Deposition of Eosinophil-Granule Major Basic Protein in Atopic Dermatitis

Leiferman, Kristin M.; Ackerman, Steven J.; Sampson, Hugh A.; Haugen, H. S.; Venencie, Pierre Y.; Gleich, Gerald J.

doi:10.1056/nejm198508013130502

Cited by 394 publications

(180 citation statements)

References 29 publications

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“…9 Assessment of eosinophil involvement in disease should not be based simply on the number of eosinophils present because intact eosinophils may not be evident; i.e., tissues should be examined for evidence of eosinophil degranulation. 23,24 Hematoxylin and eosin staining often fails to show the presence of eosinophil granules and extracellular granule proteins. Previous studies on cardiac tissue have shown the advantages of immunofluorescence staining over light microscopy for accurately visualizing eosinophils and their granules or extracellular proteins (Chau E and others, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

“…21,22 Prior studies of diseased tissues have shown extensive MBP deposition in the absence of intact tissue eosinophils. 23,24 By using an immunofluorescence technique for the colocalization of eosinophil granule MBP and P. brasiliensis, we tested the hypothesis that eosinophil infiltration and degranulation regularly occur in tissues from patients with paracoccidioidomycosis.…”

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confidence: 99%

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Localization of eosinophil granule major basic protein in paracoccidioidomycosis lesions.

Wagner

Franco

Kephart

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. Paracoccidioidomycosis is a chronic granulomatous disease caused by the fungus Paracoccidioides brasiliensis. Although eosinophils have long been associated with the immune defense against helminths, the role of eosinophils in the immune response to fungal diseases is not as well studied. The eosinophil granule major basic protein is toxic to helminths and mammalian cells in vitro, and its release has been used as a marker of eosinophil localization and degranulation. To determine whether eosinophil infiltration and degranulation, as evidenced by the deposition of major basic protein, occur in lesions of P. brasiliensis, we used an immunofluorescence technique to localize the P. brasiliensis organisms and eosinophils and major basic protein. Initially, all tissues were stained with polyclonal antibody to major basic protein; subsequently, colocalization of major basic protein and P. brasiliensis by double staining with mouse and rabbit antibodies, respectively, was performed. Nine biopsy tissues from seven patients were analyzed. All nine biopsies showed infiltration of intact eosinophils using both the monoclonal and the polyclonal anti-major basic protein antibodies, along with the presence of P. brasiliensis. Furthermore, using the polyclonal antimajor basic protein antibody, nine of nine tissues showed extracellular major basic protein deposition (granular or diffuse fluorescence staining outside of intact eosinophils). The double staining procedure using the anti-major basic protein monoclonal antibody showed extracellular deposition in five of eight biopsies; in these five biopsies, approximately 60% of the areas containing P. brasiliensis had extracellular major basic protein deposited on the organisms. These observations support the hypothesis that the eosinophil, through toxic granule proteins such as major basic protein, participates in the pathophysiology of paracoccidioidomycosis.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Localization of eosinophil granule major basic protein in paracoccidioidomycosis lesions.

Wagner

Franco

Kephart

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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“…In some patients the eosinophil infiltrate was not found by hematoxylin-eosin staining, since cells were completely degranulated and seen only by means of immunohistochemistry or electron microscopy. Accordingly, significant deposits of eosinophil-derived MBP and EDN/EPX could be detected in the eczematous skin of patients by immunohistochernical techniques, as a sign of eosinophil degranulation at the site of inflammation (22,23), Moreover, a correlation between disease activity and deposition of eosinophil granule content could be suggested (23), Late-phase reactions Similar findings were obtained in investigating the "late-phase reaction" (LPR) upon provocation with allergens by the skin chamber technique (6), Because of the mode of induction, however, the pattern of eosinophil-derived granule proteins is comparable with, but not identical to, findings in patients with AD, Nevertheless, the experimental LPR, as a model system, represents a useful tool for a better understanding of pathophysiologic principles which may also be important in AD (23), Hence a significant infiltration of basophils and, particularly, of eosinophils in the skin was detected, characteristically within 6-8 h after local allergen challenge, A mononuclear cellular infiltrate was detected after almost 24 h. During this interval most of the eosinophils were degranulated or even completely destroyed (6,23). As reported recently, a significant increase in the number of activated, EG2-positive eosinophils was observed in LPRs of nasal mucosa within 24 h following intranasal challenge of patients with allergic rhinitis with Phleum pratense (8), Moreover, these findings correlated significantly with the expression of mRNA for Th2 cytokines, particularly for lL-5.…”

Section: Eosinophilic Granulocytes and Admentioning

confidence: 99%

The role of eosinophils in the pathogenesis of atopic dermatitis ‐ eosinophil granule proteins as markers of disease activity

Kapp

1993

Allergy

156

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Currently, there is a large body of evidence that atopic dermatitis (AD) has an Immunologic basis. Atopy‐specific helper T cells (Th2‐like T cells) may play a pathogenetic role by producing and releasing cytokines relevant for the allergic inflammation, such as IL‐4, IL‐5, and other growth factors. Eosinophils are believed to be of major importance as effector cells mediating the pathogenetically relevant late‐phase reaction which is associated with a significant destruction of the surrounding tissue. Accordingly, a significant preactivation of peripheral blood eosinophils was detected in AD patients, leading to an enhanced susceptibility of these cells to distinct stimuli such as IL‐5. Toxic proteins, such as eosinophil cationic protein (ECP), contained in the matrix and the core of secondary granules of eosinophils, may play an important role by propagating the allergic inflammatory process and by modulating the immune response. The pathogenetic role of eosinophils in AD is further supported by the detection of these proteins in the eczematous skin of patients. Furthermore, recent data point to a significant correlation between disease activity and deposition of eosinophil granule content: ECP serum levels were significantly increased in AD patients. In addition, ECP levels correlated with the disease activity. Moreover, clinical improvement was associated with a decrease of both the clinical score and serum ECP levels. These data clearly indicate that activated eosinophils may play a major role in the allergic inflammatory process of AD. Therefore, modulation of eosinophil activation could prove to be an important pharmacologic modality for the treatment of AD.

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“…2,3 Eosinophils are sparse, although eosinophil products (major basic protein) are prominent. 4 Although the pathogenic role of allergy in AD has been debated for over a century, clinical studies over the past 2 decades have supported the pathogenic role of food allergy in a subset of patients with AD. [5][6][7] A recent study found that approximately 40% of children with moderate-to-severe AD attending a university dermatology clinic had food hypersensitivity.…”

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Murine model of atopic dermatitis associated with food hypersensitivity

Kleiner²,

Huang³

et al. 2001

Journal of Allergy and Clinical Immunology

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109

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Background: Atopic dermatitis (AD) is an eczematous skin eruption that generally begins in early infancy and affects up to 12% of the population. The cause of this disorder is not fully understood, although it is frequently the first sign of atopic disease and is characterized by an elevated serum IgE level, eosinophilia, and histologic tissue changes characterized early by spongiosis and a CD4 + T H 2 cellular infiltrate. Hypersensitivity to foods has been implicated as one causative factor in up to 40% of children with moderate-to-severe AD. Objective: The purpose of this study was to establish a murine model of food-induced AD. Methods: Female C3H/HeJ mice were sensitized orally to cow's milk or peanut with a cholera toxin adjuvant and then subjected to low-grade allergen exposure. Histologic examination of skin lesions, allergen-specific serum Ig levels, and allergen-induced T-cell proliferation and cytokine production were examined. Atopic dermatitis (AD) is a form of eczema that generally begins in early infancy and is characterized by extreme pruritus, chronically relapsing course, and distinctive distribution. AD is often the first sign seen in a child who is prone to atopic disease, with 50% of all AD developing in the first year of life and 80% developing by 5 years of age. 1 In chronic skin lesions the epidermis has moderate-to-marked hyperplasia, with elongation of the rete ridges and prominent hyperkeratosis. Spongiosis is variable, and the numbers of mast cells and Langerhans cells are significantly increased. 2,3 Eosinophils are sparse, although eosinophil products (major basic protein) are prominent. 4 Although the pathogenic role of allergy in AD has been debated for over a century, clinical studies over the past 2 decades have supported the pathogenic role of food allergy in a subset of patients with AD. 5-7 A recent study found that approximately 40% of children with moderate-to-severe AD attending a university dermatology clinic had food hypersensitivity. 7 Other studies delineating the role of IgE-bearing antigen-presenting cells in establishing T H 2 lymphocytic responses 8 and demonstrating the predominant T H 2-lymphocytic infiltrate in acute eczematous lesions 9 have provided further support for the pathogenic role of allergy in AD.Animal models provide powerful tools for dissecting pathogenic mechanisms responsible for various disorders. A number of murine models of asthma have been developed in the past several years that have contributed greatly to our understanding of the immunopathogenesis of allergen-induced asthma. 10-12 Models of antigenassociated AD have been reported in cats and dogs, but because of difficulties with consistent induction of ADlike eruptions and high expense, they have not been widely studied. 13,14 A mouse strain, NC/Nga, has been reported that spontaneously has an AD-like skin lesion and IgE hyperproduction, presumably triggered by environmental factors. 15 More recently, a murine model of AD was described in which BALB/c mice were sensitized to ovalbumin (OVA...

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Dermal Deposition of Eosinophil-Granule Major Basic Protein in Atopic Dermatitis

Cited by 394 publications

References 29 publications

Localization of eosinophil granule major basic protein in paracoccidioidomycosis lesions.

Localization of eosinophil granule major basic protein in paracoccidioidomycosis lesions.

The role of eosinophils in the pathogenesis of atopic dermatitis ‐ eosinophil granule proteins as markers of disease activity

Murine model of atopic dermatitis associated with food hypersensitivity

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