Corticotropin-Releasing Hormone and Its Structurally Related Urocortin Are Synthesized and Secreted by Human Mast Cells

Many neuropsychiatric diseases still elude full understanding and effective therapy. It has become increasingly obvious that some of the prevailing explanations of their pathology are overly simplistic since only a small fraction of patients appear to be Stress activates the hypothalamic-pituitary-adrenal axis through CRH, leading to production of glucocorticoids that down-regulate immune responses. However, acute stress also has proinflammatory effects. We previously showed that re- straint stress, as well as CRH and its structurally related uro- cortin (Ucn), could activate mast cells and trigger mast cell- dependent vascular permeability. Here we show for the first time that human cord blood-derived cultured mast cells (hCBMC) at 10 wk, but not at 2 wk, are immunocytochemically positive for CRH and Ucn; human leukemic mast cells are weakly positive for both peptides. The ability of these mast cells to synthesize CRH and Ucn was confirmed by showing mRNA expression with RT-PCR. hCBMC (8 –14 wk) synthesize and store 1–10 ng/106 cells (10–20

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