Expression of histidine decarboxylase in melanocytes of the human skin

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Highlights

  • HDC-positive and CK14-negative cells were present in basal layer of the epidermis.

  • Mast cell tryptase was not immunoreactive with epidermal HDC-positive cells.

  • HDC-positive and CK14-positive cells immunohistochemically reacted with tyrosinase.

  • HDC mRNA and protein were detected in cultured normal human epidermal melanocytes.

Abstract

Histamine-producing cells include storage-type cells (e.g., mast cells and basophils), which store histamine intracellularly, and inducible-type cells (e.g., keratinocytes and macrophages), which induce histidine decarboxylase (HDC, a key enzyme for histamine biosynthesis) activity but do not have a storage pool of histamine. Most of the studies focused on identifying HDC-expressing cells by using cultured cells, and few on investigating the localization of HDC by using skin tissues. Hence, this study conducted immunohistochemical studies using human healthy skin samples. HDC-positive and cytokeratin 14 (a marker of basal keratinocytes)-negative cells were present around the basal layer of the epidermis. These cells did not immunohistochemically react with mast cell tryptase but expressed tyrosinase (a key enzyme for melanin biosynthesis) and microphthalmia-associated transcription factor (MITF, a transcription factor controlling the expression of tyrosinase genes). Melanin granules were clearly observed around HDC-positive and MITF-positive cells. Moreover, HDC mRNA and protein were both detected in cultured normal human epidermal melanocytes. In conclusion, HDC-positive and cytokeratin 14-negative cells around the basal layer of the epidermis are melanocytes.

Introduction

Histamine is a physiologically active amine widely distributed in the peripheral and central nervous systems. It is involved in inflammation, allergic reaction, gastric acid secretion, itching, and neurotransmission in vivo. Furthermore, histamine is stored in the granules of storage-type histamine-producing cells, namely, mast cells and basophils. Schayer and Ganley (1959) and Kahlson et al. (1960) reported the presence of a different type of histamine-producing cell in which the biosynthetic activity of histamine is recognized but the pool for storing itself remains unidentified [1,2]. Histidine decarboxylase (HDC), which is a key enzyme for histamine synthesis, is induced by lipopolysaccharides and cytokines such as interleukin (IL)-1β, tumor necrosis factor-α, granulocyte macrophage-colony stimulating factor, IL-18, and IL-12 [3,4]. Currently, T cells [5,6], B cells [5], macrophages [[7], [8], [9]], neutrophils [10], keratinocytes [11,12], and vascular endothelial cells [13] are regarded as HDC-inducing cells (inducible histamine-producing cells).

Exposure to surfactants or intradermal injection of α-melanocyte–stimulating hormone increases mouse epidermal HDC [14,15], chronic pruritus with unknown cause induces monkey epidermal HDC [16], and atopic dermatitis increases human epidermal HDC [17]. However, HDC-expressing cells have not yet been sufficiently assessed using skin tissue. We report a novel finding obtained from examining the localization of HDC in human healthy skin samples.

Section snippets

Subjects

Skin of three healthy subjects (age range: 18–40 years, two males and one female) was biopsied from a healthy part of their upper arm at a Russian hospital and provided by Obio LLC (El Segundo, CA). Informed consent was obtained for experimentation with all human subjects. The Ethics Committee for Human Research (Hoyu Co., Ltd., Aichi, Japan) approved this study.

Immunohistochemical staining

The biopsied skin samples were fixed in buffered formalin, embedded in paraffin, and sectioned at 5 μm thick. After the samples were

Expression of HDC in the skin

The epidermis is primarily composed of keratinocytes, which comprise >90% of the epidermal cells; other epidermal cells include melanocytes, Langerhans cells, and Merkel cells. In healthy subjects, HDC-immunoreactive cells were detected around the basal layer of the epidermis (white arrows in Fig. 1a). To examine whether the HDC-immunoreactive cells are keratinocytes, we assessed the immunoreactivities of CK14 (a marker of undifferentiated keratinocytes [18]) and CK10 (a marker of suprabasal

Discussion

This study found HDC-positive and CK14-negative cells in the skin of healthy subjects. The immunohistochemical results of collagen IV revealed that these cells were present in the epidermis. Meanwhile, the immunoreactivity of mast cell tryptase [AA1] was exclusively observed only in the dermis and was not detected in the epidermal HDC-positive cells, suggesting that the epidermal HDC-positive and CK14-negative cells are not mast cells. Furthermore, the cells expressed melanocyte-specific

Conflicts of interest

Y.I. and M.F. are employed by Hoyu Co., Ltd. who financially supported the research.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

This work was financially supported by Hoyu Co., Ltd. We would like to thank Ai Kobayashi of Hoyu Co., Ltd. For cell culture and the kind support on tissue staining and Masaki Yoshida of Kracie Home Products, Ltd. For constructive comments on the manuscript.

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