Corticotropin-releasing hormone and its structurally related urocortin are synthesized and secreted by human mast cells.
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 restraint stress, as well as CRH and its structurally related urocortin (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 microg/g) of both CRH and Ucn detected by ELISA of cell homogenates. Stimulation of IgE-sensitized hCBMC with anti-IgE results in secretion of most CRH and Ucn. These findings indicate that mast cells are not only the target, but also a potential source of CRH and Ucn that could have both autocrine and paracrine functions, especially in allergic inflammatory disorders exacerbated by stress.
Department of Pharmacology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Duraisamy
D
Kempuraj
Nikoletta G
NG
Papadopoulou
Michael
M
Lytinas
Man
M
Huang
Kristiana
K
Kandere-Grzybowska
Bhuvaneshwari
B
Madhappan
William
W
Boucher
Spyridon
S
Christodoulou
Achilles
A
Athanassiou
Theoharis C
TC
Theoharides
D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005312:Fetal Blood / Q000166:cytology; D015870:Gene Expression; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology; D007150:Immunohistochemistry; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012697:Serine Endopeptidases / Q000378:metabolism; D013312:Stress, Physiological / Q000276:immunology; D053802:Tryptases; D054832:Urocortins
D012333:RNA, Messenger; D054832:Urocortins; D007073:Immunoglobulin E; D003346:Corticotropin-Releasing Hormone; D012697:Serine Endopeptidases; D053802:Tryptases