Assessment of eosinophil and neutrophil participation in atopic dermatitis: Comparison with the IgE-mediated late-phase reaction

Ott, Nancy L.; Gleich, Gerald J.; Peterson, Ellen A.; Fujisawa, Takao; Sur, Sanjiv; Leiferman, Kristin M.

doi:10.1016/0091-6749(94)90078-7

Cited by 93 publications

(67 citation statements)

References 36 publications

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“…5). These findings raise the possibility that the improvement of skin lesions by SUN-C8257 in NC/Nga mice might be due to its ability to inhibit eosinophil infiltration, since eosinophils are probably implicated in the pathogenesis of AD [25, 26]. The other data in our own studies have shown that SUN-C8257 inhibits helminth-induced blood eosinophilia in mice (manuscript in preparation).…”

Section: Discussionmentioning

confidence: 70%

Chymase Inhibitor Improves Dermatitis in NC/Nga Mice

Watanabe

Tomimori

Saito

et al. 2002

Int Arch Allergy Immunol

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Background: Mast cell chymase is thought to participate in allergic inflammation, but its precise role remains undetermined. Inbred NC/Nga mice develop skin lesions similar to atopic dermatitis (AD) when they grow up in a conventional environment. To elucidate the possible role of chymase in AD, we examined the effect of a chymase inhibitor on skin lesions of NC/Nga mice. Methods: NC/Nga mice were given the chymase inhibitor SUN-C8257 daily at 150 mg/kg/day with drinking water, and the severity of the dermatitis was evaluated on day 35 of the experiment. The role of chymase in dermatitis was further investigated in vitro and in vivo using recombinant mouse mast cell protease-4 (mMCP-4). Results: Administration of SUN-C8257 significantly reduced the clinical skin and histological score in NC/Nga mice. SUN-C8257 also inhibited the accumulation of inflammatory cells, such as eosinophils and mast cells, in the affected lesions in this model. mMCP-4 stimulated eosinophil migration in vitro, and intradermal injection of the enzyme resulted in a significant accumulation of inflammatory cells, including eosinophils, at the injection site. Thus amelioration of the skin lesions in NC/Nga mice by SUN-C8257 might be, at least in part, due to the suppression of cell infiltration in the lesions. Conclusions: Mast cell chymase may contribute to the pathogenesis of AD, and SUN-C8257 will be beneficial to the treatment of the skin disorder.

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Section: Discussionmentioning

confidence: 70%

Chymase Inhibitor Improves Dermatitis in NC/Nga Mice

Watanabe

Tomimori

Saito

et al. 2002

Int Arch Allergy Immunol

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“…Based on prior studies, other eosinophil granule proteins (EDN, ECP, and EPO) are likely also released in this disease. 34 Knowledge of the presence of eosinophils and eosinophil proteins furthers our understanding of the pathology of the P. brasiliensis lesions and the overall immune response of the patient. Increased eosinophils in the blood or tissue lesions may be a prognostic indicator and may provide another possible target for disease treatment.…”

Section: Discussionmentioning

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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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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“…Previous studies on AE have shown a correlation between the severity of disease and the peripheral blood eosinophil count as well as between the severity of disease and the eosinophil-derived protein in the serum, urine and tissue, such as eosinophil cationic protein (ECP), major basic protein (MBP), and eosinophil-derived neurotoxin/eosinophil protein X (EDN/EPX) [43,44,45]. In one of the studies, an increase in the number of EG2+ cells in AE lesion was demonstrated; however, no significant correlation was detected between the number of EG2+ cells and the peripheral blood eosinophil count [46].…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of RANTES, CCR3 and CCR5 in the Lesional Skin of Patients with Atopic Eczema

Kato

Pawankar

Kimura

et al. 2006

Int Arch Allergy Immunol

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Background: Atopic eczema (AE) is a relapsing inflammatory disease based on IgE sensitization and characterized by peripheral blood eosinophilia and eosinophil infiltration into the lesional skin. In the patch test reaction of AE by allergens, an increased infiltration of activated eosinophils has been demonstrated peaking at 24–48 h. Regulated on activation normal T cell expressed and secreted (RANTES/CCL5) is a chemokine that induces eosinophil migration, and CCR3 and CCR5 are the receptors of RANTES. Objective: In order to further clarify the pathomechanisms of eosinophil infiltration in ongoing chronic inflammation in the skin of patients with AE and its relation to disease severity, we examined the expression of RANTES and its receptors CCR3 and CCR5 in challenged and unchallenged lesional skin of AE. Methods: We examined the number of RANTES+ cells, CCR3+ cells, CCR5+cells, activated (EG2+) eosinophils and CD3+ T cells in normal skin of healthy volunteers, and in challenged lesional skin (24 h after mite patch test) as well as unchallenged lesional skin of AE patients by immunohistochemistry. The cellular source of RANTES, CCR3 and CCR5 was analyzed by double immunohistochemistry using specific antibodies to RANTES, CCR3 or CCR5, and antibodies to ECP (EG2) or CD3. Results: The numbers of RANTES+ cells, CCR3+ cells, CCR5+ cells, EG2+ cells and CD3+ cells were all significantly increased in challenged (mite patch-tested) lesional skin of AE patients as compared to those in unchallenged lesional skin and normal skin. The numbers of these cells in unchallenged lesional skin were greater than those in normal skin. The number of EG2+ cells in the unchallenged lesional skin correlated with both the peripheral blood eosinophil count and the SCORAD index. The number of EG2+ cells in challenged lesional skin correlated with the number of CCR5+ cells. Activated eosinophils and T cells expressed RANTES and various proportions of these cells were CCR3+ and CCR5+ in both challenged and unchallenged lesional skin. Conclusion: Taken together, these results suggest that RANTES as well as its receptors CCR3 and CCR5 may play important roles in the orchestration of eosinophil infiltration in ongoing chronic inflammation in AE, and also reflect the severity of disease.

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Assessment of eosinophil and neutrophil participation in atopic dermatitis: Comparison with the IgE-mediated late-phase reaction

Cited by 93 publications

References 36 publications

Chymase Inhibitor Improves Dermatitis in NC/Nga Mice

Chymase Inhibitor Improves Dermatitis in NC/Nga Mice

Localization of eosinophil granule major basic protein in paracoccidioidomycosis lesions.

Increased Expression of RANTES, CCR3 and CCR5 in the Lesional Skin of Patients with Atopic Eczema

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