Mechanisms of nonimmunological histamine and tryptase release from human cutaneous mast cells.
BACKGROUND
If mast cells are stimulated they release multiple mediators that delineate markers for immunologic and nonimmunologic reactions; histamine and tryptase are the two best known. Although histamine can be assayed in plasma, it is a nonspecific marker with a very short half-life. Tryptase has a longer half-life, but its release has not been proven to be specific for anaphylaxis. The authors investigated the mechanisms of nonimmunologic histamine release from human cutaneous mast cells to understand the mechanisms of mediator release and to determine whether tryptase was specific for allergic mediated activation.


METHODS
Dispersed mast cell suspensions isolated from neonatal foreskins underwent challenge with vancomycin, calcium ionophore A23187, morphine, and atracurium, and histamine tryptase release was measured. The effects of calcium and magnesium, along with phospholipase C and phospholipase A2 inhibitors, also were investigated.


RESULTS
Tryptase and histamine both were released by the known nonimmunologic stimuli (pharmacologic agents used in the current study; r2 = 0.6). Furthermore, vancomycin- and atracurium-induced histamine release was calcium dependent. Phospholipase C and phospholipase A2 inhibitors decreased vancomycin-induced histamine release, but not calcium ionophore A23187-induced release.


CONCLUSIONS
Tryptase is not a specific marker of mast cell activation (ie., anaphylaxis), and signaling mechanisms for mast cell activation involve activation of phospholipase C and phospholipase A2 pathways that are also involved in other cellular activation mechanisms.
Veien
M
M
Department of Anesthesiology, Emory University School of Medicine, Emory Healthcare, Atlanta, Georgia, USA.
Szlam
F
F
Holden
J T
JT
Yamaguchi
K
K
Denson
D D
DD
Levy
J H
JH
D016718:Arachidonic Acid / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D015550:Cell Degranulation; D002478:Cells, Cultured; D053818:Chymases; D003600:Cytosol / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006636:Histamine Release / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000201:enzymology / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D054467:Phospholipases A2; D012697:Serine Endopeptidases / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D053802:Tryptases; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D016718:Arachidonic Acid; D000001:Calcimycin; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases; D002118:Calcium