The Expression of Histamine Receptors in Skin Lesions of MRL/MPlpr/ lpr Mice

Takashi Yoshimasu,Fukumi Furukawa,Nobuo Kanazawa,Naoya Mikita

doi:10.2174/1874372200802010083

Abstract

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease accompanied with systemic organs dis- order including skin changes. The MRL/MP-lpr/lpr (MRL/l) mouse is a model of human LE. MRL/l mice skin lesions ex- hibit a decreased activity in histamine-N-methyltransferase (HMT) and impaired histamine metabolism. In order to clarify the role of histamine receptors (HRs) including H1R, H2R and H3R in MRL/l skin lesions, the relationship between HRs and skin lesions was assessed by immunohistochemical staining and RT-PCR methods. The expression of H2R was seen in the non-lesional skin of 2-month-old (mo) MRL/l mice; H2R expression continued for a couple of months, and then de- creased in the skin lesions of 5-mo MRL/l mice. In MRL/l skin lesions, a dense mast cell infiltration expressed H2R was seen. In conclusion, an increased expression of H2R in mast cells may be associated with histamine metabolism in skin le- sions from MRL/l mice.

Highlights

The etiology of human LE is not fully understood, skin lesions have a number of infiltrating T cells and their related mediators
MRL/l mice show immune complex glomerulonephritis, arteritis, arthritis, anti-DNA antibody and spontaneous LE-like lesions with IgG deposits at the dermoepidermal junction [1, 8]. These clinical findings are largely similar to human systemic lupus erythematosus (SLE), thereby MRL/l mice are supposed to be an excellent model of Systemic lupus erythematosus (SLE)
We focused on the relationship of the expression of histamine receptors (HRs) and skin lesions

Summary

Introduction

The etiology of human LE is not fully understood, skin lesions have a number of infiltrating T cells and their related mediators. The MRL/l mouse is a model for the spontaneous development of skin lesions similar to those associated with human LE [1,2,3]. In skin lesions from MRL/l mice, a decreased activity in histamine-N-methyltransferase (HMT) is reported and impaired histamine metabolism is supposed to be a particular biochemical feature of the MRL/l skin [4]. In human SLE, irrespective of fresh lesions or perilesional sites, the HMT activity of lesions is much lower than that of controls and the decreased activity plays a particular role in the development of immune-complex– medicated skin lesions [5]. In order to clarify the role of histamine receptors (HRs) in skin lesions from MRL/l mice, we determined the relationship between HRs and the development of skin lesions

Methods

Results

Conclusion