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Expression of a prostaglandin D2 receptor, CRTh2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) on human mast cells and potential relevance in allergic diseases
Allergy, Asthma & Clinical Immunology volume 6, Article number: P22 (2010)
Prostaglandin D2 (PGD2) has long been implicated in allergic diseases such as asthma by contributing to bronchoconstriction, vasodilation, and vascular permeability. Recently, cloning of a second novel PGD2 receptor CRTh2, led to a greater understanding of the physiological and pathophysiological implications of PGD2. PGD2 signaling through DP1 and CRTh2 (DP2) mediates different and often opposite effects in many cell types of the immune system. Although mast cells (MC) are the largest source of PGD2 in the body, there is lack of information about their expression and the role of PGD2 receptors.
Materials and methods
CRTh2 transcripts and protein expression in two human mast cell lines, HMC-1 and LAD2, and two primary cultured human MC, cord blood-derived MC (CBMC) and peripheral blood-derived MC (PBMC), were examined using RT-PCR and flow cytometry. Expression of CRTh2 in MC from human nasal polyps was examined using immunohistochemistry. Intracellular calcium mobilization after treatment with the CRTh2 specific agonist, 15R-15-methyl PGD2 was measured using Fluo-4NW calcium assay kit.
RT-PCR and flow cytometry showed that human MC express CRTh2. About 35% of tissue MC in nasal polyps expressed CRTh2. The CRTh2 specific agonist induced a dose dependent intracellular calcium mobilization in human MC.
Human MC express functional CRTh2. Regulation of MC mediator release and positive feedback recruitment of MC through CRTh2-mediated signaling may play an important role in allergic diseases.