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

Vol. 139, No. 3, 2006

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Original Paper

Increased Expression of RANTES, CCR3 and CCR5 in the Lesional Skin of Patients with Atopic Eczema
Yoko Kato^a, Ruby Pawankar^b, Yoichi Kimura^a, Seiji Kawana^a

Departments of
^aDermatology and
^bOtolaryngology, Nippon Medical School, Tokyo, Japan

Address of Corresponding Author

Int Arch Allergy Immunol 2006;139:245-257 (DOI: 10.1159/000091170)

Key Words

Atopic eczema
RANTES
CCR3
CCR5
Eosinophil
T cell
Mite allergen
Patch test

Abstract

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.

Author Contacts

Correspondence to: Prof. Ruby Pawankar
Department of Otolaryngology
Nippon Medical School, 1-1-5 Sendagi
Bunkyo-ku, 113-8603 Tokyo (Japan)
Tel./Fax +81 3 5802 8177, E-Mail Pawankar_Ruby/ent@nms.ac.jp

Article Information

Received: June 1, 2005
Accepted after revision: October 17, 2005
Published online: January 30, 2006
Number of Print Pages : 13
Number of Figures : 3, Number of Tables : 2, Number of References : 46

Medline Abstract (ID 16449815)

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