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Human heart as a shock organ in anaphylaxis

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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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Authors and Affiliations

  1. Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy

    Gianni Marone, Arturo Genovese, Gilda Varricchi & Francescopaolo Granata

  2. Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy

    Gianni Marone & Arturo Genovese

  3. Department of Translational Medical Sciences, University of Naples Federico II, Via S. Pansini 5, 80131, Napoli, Italy

    Gianni Marone

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  1. Gianni Marone
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  2. Arturo Genovese
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  4. Francescopaolo Granata
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Correspondence to Gianni Marone.

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The authors states that there are no conflicts of interest.

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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