Mast Cell Degranulating (MCD) Peptides

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Introduction

Mast Cell Degranulating (MCD) peptide is a 22-amino acid bicyclic peptide with two intramolecular disulfide pairs forming a spherical globule isomer and it has a high number of positive charges. MCD peptide is strong, naturally occurring histamine secretagogue at low concentrations that also has a known anti-inflammatory activity in vivo at higher concentrations. MCD peptide is thought to be involved in allergic and inflammatory processes related to the type I hypersensitivity reaction, which is caused by mast cell degranulation and the subsequent release of histamine and other inflammatory mediators.

Mechanism of action

MCD peptide can release histamine from mast cells when no IgE is present. It is assumed that this occurs because MCD peptide possesses basic and hydrophobic clusters of amino acids that resemble and mimic the portion of the IgE molecules binding site to the FcεRI mast cell receptor.
MCD peptide at low concentrations also releases histamine from mast cells when IgE is present. It is assumed that at low concentrations a single MCD peptide molecule acts as an “allergen” by cross-linking two adjacent IgE molecules at their Fab portions, thus activating the FcεRI receptor and causing the cell to degranulate and release histamine. The anti-inflammatory activity of MCD peptide at concentrations higher than those that release histamine has been proposed to be due to the formation of intermolecular disulfide complexes between MCD peptide and IgE.

Application of MCD peptide

Because of these unique immunologic properties, MCD peptide may serve as a useful tool for studying secretory mechanisms of inflammatory cells such as mast cells, basophils, and leukocytes, leading to the design of compounds with therapeutic potential. The regulatory action for such an agent as MCD peptide could probably modulate release so that mast cells do not act in an inflammatory manner but as helpers in a protective host inflammatory defense mechanisms and in other mast cell related functions such as angiogenesis, an important process in tissue repair and tumor growth.

References

1. Angeliki Buku. (1999). Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation. Peptides, 20(3), 415-420.
2. B. Jasani, G. Kreil, B.F. Mackler, D.R. Stanworth. (1979). Further studies on the structural requirements for polypeptide mediated histamine release from rat mast cells. Biochem J, 181, 623-632.