Human mast cells in the neurohormonal network: expression of POMC, detection of precursor proteases, and evidence for IgE‐dependent secretion of alpha‐MSH

Human mast cells have been shown to release histamine in response to the neuropeptide α‐melanocyte‐stimulating hormone (alpha‐MSH), but it is unknown whether these cells express proopiomelanocortin (POMC) or POMC‐derived peptides. We therefore examined highly purified human skin mast cells and a leukemic mast cell line (HMC‐1) for their ability to express POMC and members of the prohormone convertase (PC) family known to process POMC. Furthermore, we investigated whether these cells store and secrete α‐MSH. RT‐PCR analysis revealed that both skin mast cells and HMC‐1 cells express POMC mRNA and protein. Expression of the POMC gene at the RNA level in HMC‐1 cells could be confirmed by Northern blotting. Transcripts for both PC1 and furin convertase were detectable in skin‐derived mast cells and HMC‐1 cells, as shown by RT‐PCR. In contrast, PC2 transcripts were detected only in skin mast cells, while transcripts for PACE4 were present only in HMC‐1 cells. Radioimmunoassays performed on cell lysates and cell culture supernatants from human skin‐derived mast cells disclosed immunoreactive amounts of alpha‐MSH in both fractions. Stimulation with an anti‐IgE antibody significantly reduced intracellular alpha‐MSH and increased extracellular levels, indicating IgE‐mediated secretion of this neuropeptide. Our findings show that human mast cells are active players in the cutaneous POMC system. Mast cell‐derived alpha‐MSH may contribute to cutaneous hyperpigmentation as seen in patients with urticaria pigmentosa. Moreover, IgE‐dependent release of alpha‐MSH suggests an immunomodulatory role of this neurohormone during inflammatory and allergic reactions of the skin.