Summary
Anaphylaxis is a potentially fatal, immediate hypersensitivity reaction. Mast cells and basophils, by elaborating vasoactive mediators and cytokines, are the main primary effector cells of anaphylaxis. Mast cells have been identified in human heart between myocardial fibers, perivascularly, in the adventitia, and in the arterial intima. Mast cells isolated from human heart tissue (HHMC) of patients undergoing cardiac transplantation express high affinity immunglobulin E (IgE) receptors (FcεRI), C3a, C5a, and kit receptors (KIT). Anti-IgE, anti-FcεRI, and immunoglobulin superallergens induce in vitro secretion of preformed mediators (histamine, tryptase, chymase, and renin) and the de novo synthesis of cysteinyl leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) from HHMC. Complement is activated and anaphylatoxin forms during anaphylaxis. C5a and C3a cause the in vitro release of histamine and tryptase from HHMC. Therapeutic (general anesthetics, protamine, etc.) and diagnostic agents (radio contrast media, etc.), which can cause anaphylactoid reactions, activate HHMC in vitro. Low concentrations of histamine and cysteinyl leukotrienes given to subjects undergoing diagnostic catheterisation caused significant systemic and coronary hemodynamic effects. These data indicate that human heart mast cells and their mediators play a role in severe anaphylactic reactions.
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Abbreviations
- C3aR:
-
C3a receptor
- C5aR:
-
C5a receptor
- CH:
-
Control heart
- CBF:
-
Coronary blood flow
- CVR:
-
Coronary vascular resistance
- CysLT2:
-
Cysteinyl leukotriene receptor 2
- CysLT1:
-
Cysteinyl leukotriene receptor 1
- DCM:
-
Dilated cardiomyopathy
- ECP:
-
Eosinophil cationic protein
- FcɛRI:
-
High affinity immunglobulin E receptors
- HHMC:
-
Mast cells isolated from human heart tissue
- ICM:
-
Ischemic cardiomyopathy
- IgE:
-
Immunglobulin E
- LTC4 :
-
Cysteinyl leukotriene C4
- LTD4 :
-
Cysteinyl leukotriene D4
- LV:
-
Left ventricular
- MBP:
-
Major basic protein
- PAF:
-
Platelet-activating factor
- PGD2 :
-
Prostaglandin D2
- SCF:
-
Stem cell factor
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Acknowledgments
This paper is dedicated to Professor Johannes Ring in recognition of his pioneering studies on anaphylaxis. This work was supported in part by grants from the Ministero dell’Istruzione, Università e Ricerca (MIUR; Marone G. and Genovese A.), the Istituto Superiore di Sanità AIDS Project „Role of basophils in HIV-1 infection“ (Marone G.), Regione Campania „CISI-Lab Project“ and CRÈME Project (Marone G.). Marone G. is the recipient of the Paul Ehrlich Award 2011.
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Marone, G., Genovese, A., Varricchi, G. et al. Human heart as a shock organ in anaphylaxis. Allergo J Int 23, 60–66 (2014). https://doi.org/10.1007/s40629-014-0007-3
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DOI: https://doi.org/10.1007/s40629-014-0007-3