The involvement of eosinophils in the patch test reaction to aeroallergens in atopic dermatitis: its relevance for the pathogenesis of atopic dermatitis

Abstract

Atopic dermatitis (AD) is considered a T-cell mediated disease. Activated T-cells, mainly of the CD4-subtype, are abundantly present in lesional AD skin. Although not many intact eosinophils are present, deposits of eosinophil derived major-basic-protein (MBP) and eosinophil-cationic-protein (ECP) suggest eosinophil involvement. After patch testing AD patients with aeroallergens, an eczematous reaction develops after 24-48 hr at the site of application. This patch test reaction shows macroscopic resemblance to lesional AD skin and does not take place in normal individuals, asthma and allergic rhinitis patients. Lymphocytes together with eosinophils infiltrate into the dermis 2-6 hr after allergen application. Twenty-four to forty-eight hours after patch testing, eosinophils are in an activated state since they release ECP (being EG2-positive). At this point in time eosinophils have also infiltrated the epidermis. Here they are EG2-negative. Forty-eight to seventy-two hours after patch testing the eczematous reaction decreases. This coincides with disappearance of eosinophils from both the dermis and the epidermis; then, a dendritic staining pattern can be observed in the epidermis with anti-eosinophil peroxidase. Thus, eosinophils infiltrate the dermis and epidermis after patch testing AD patients with aeroallergens and release part of their granular constituents. Recent in vitro investigations revealed that eosinophils from the circulation of AD patients react more powerfully in in vitro test systems such as chemiluminescence, chemotaxis and endothelial adherence and transmigration. It is very likely that this activated (= primed) state is caused by the influence of lymphocyte-derived cytokines like IL-3, IL-5 and GM-CSF, since activated lymphocytes in the circulation (and tissue) may release these cytokines. The primed state of the eosinophils may facilitate tissue infiltration. The subsequent activation of eosinophils within the tissue leading to mediator release and the function of these mediators need to be further elucidated. The close similarity between the cellular events after a patch test reaction to aeroallergens in AD patients and those present in lesional AD skin suggests that the patch test reaction may be a helpful in vivo model to study the pathogenesis of AD. The prominent involvement of lymphocytes and eosinophils in this reaction also suggests some similarity with late phase reactions (LPR) observed in the skin after intracutaneous allergen challenge.

In vivo transfection of a cis element ‘decoy’ against signal transducers and activators of transcription 6 (STAT6)-binding site ameliorates IgE-mediated late-phase reaction in an atopic dermatitis mouse model

“…Recently, IgE-mediated late-phase reaction is thought to be mainly associated with the pathogenesis of AD. [4][5][6] We have established the eczematous skin reaction induced by anti-DNP-IgE antibody and DNFB as an AD model mouse. [7][8][9] STAT6 is known as a regulator of IL-4-dependent immune responses.…”

“…[4][5][6] To clarify the pathomechanism underlying the development of eczematous skin lesions in AD, we established the eczematous skin reaction induced in mice by the intravenous injection of monoclonal anti-dinitrophenyl (DNP)-IgE antibody and subsequent skin testing with 2,4-dinitrofluorobenzene (DNFB) and analyzed these skin reactions as AD mouse model. [7][8][9] We previously demonstrated that mast cells and inflammatory cells other than T cells are thought to play an important role in these IgE-mediated biophasic reaction; 9 however, it remains unclear as to whether Th2-type cytokines, IL-4, IL-5 or IL-13, play a role in the induction of the IgE-mediated reaction.…”

Inhibition of Allergic Dermal Inflammation by the Novel Imidazopyridazine Derivative TAK-427 in a Guinea Pig Experimental Model of Eczema

“…Histopathological studies shown that the skin lesions of atopic dermatitis are characterized by acanthosis and spongiosis in the epidermis, predominant infiltration by CD1 ϩ cells and activated CD4 ϩ T cells in the dermis, and extensive deposition of eosinophil granule proteins, such as eosinophil major basic protein and eosinophil cationic protein (Leiferman et al, 1985;Bruijnzeel et al, 1993). In addition, serum levels of eosinophil cationic protein have been reported to correlate with the severity of disease (Tsuda et al, 1992).…”

Oral Administration ofVaccinium uliginosumL. Extract Alleviates DNCB-Induced Atopic Dermatitis in NC/Nga Mice

“…This is supported by a recent study suggesting that Th2 cytokines are involved in eosinophil recruitment. 33,34 Moreover, the suppressed degranulation of mast cells was correlated with the alleviation of the itching and scratching behavior of mice (Fig. 3).…”

“…5,20 Eosinophils play a crucial role in AD symptoms; they secrete eosinophil cationic proteins and thereby induce infiltration of other immune cells into the skin lesions. 33,34 In addition, infiltrated mast cells were degranulated to release histamine and nitric oxide, which promote severe itching. 31,32 Treatment with VU alleviated histopathological AD-like symptoms in dorsal skin, including epidermal thickening (Fig.…”