Brain mast cells act as an immune gate to the hypothalamic-pituitary-adrenal axis in dogs.
Mast cells perform a significant role in the host defense against parasitic and some bacterial infections. Here we show that in the dog, degranulation of brain mast cells evokes hypothalamic-pituitary-adrenal responses via histamine release. A large number of mast cells were found in a circumscribed ventral region of the hypothalamus, including the pars tuberalis and median eminence. When these intracranial mast cells were passively sensitized with immunoglobulin E via either the intracerebroventricular or intravenous route, there was a marked increase in the adrenal cortisol secretion elicited by a subsequent antigenic challenge (whether this was delivered via the central or peripheral route). Comp.48/80, a mast cell secretagogue, also increased cortisol secretion when administered intracerebroventricularly. Pretreatment (intracerebroventricularly) with anti-corticotropin--releasing factor antibodies or a histamine H(1) blocker, but not an H(2) blocker, attenuated the evoked increases in cortisol. These data show that in the dog, degranulation of brain mast cells evokes hypothalamic-pituitary-adrenal responses via centrally released histamine and corticotrophin-releasing factor. On the basis of these data, we suggest that intracranial mast cells may act as an allergen sensor, and that the activated adrenocortical response may represent a life-saving host defense reaction to a type I allergy.
Matsumoto
I
I
Department of Physiology, Nagasaki University School of Medicine, Nagasaki 852, Japan. matu-itu@net.nagasaki-u.ac.jp
Inoue
Y
Y
Shimada
T
T
Aikawa
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001921:Brain / Q000166:cytology*; D003346:Corticotropin-Releasing Hormone / Q000276:immunology; D004285:Dogs; D005260:Female; D006632:Histamine / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006854:Hydrocortisone / Q000378:metabolism; D006967:Hypersensitivity / Q000276:immunology; D007030:Hypothalamo-Hypophyseal System / Q000166:cytology / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D010913:Pituitary-Adrenal System / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D007073:Immunoglobulin E; D006632:Histamine; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone