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Septic cardiomyopathy: The Value of Immuno-histochemical Diagnostics and Role of Lipopolysaccharide Receptor (CD14)

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By P. M. Reil, T. T. Maghiar, N. Vîlceanu, A. Pascalau, Claudia Teodora Judea Pusta, F. Marcu , Simona Cavalu and Ovidiu Pop

The aim of this our study was to determine any significance of the mCD14 and sCD14 levels in the septic cardiomyopathy, and to evaluate the correlation with lipopolysaccharide-binding protein (LBP) by means of immuno-histological examinations.

(A,B) H&E normal aspects of the control group, showing cardiac muscle fibers with interstitial edema and inflammatory infiltrate. (A) Cardiac muscle fibers with small nuclei located centrally—white arrows (magnification 100×). (B) The nuclei of the fibers are enlarged in volume, revealing cellular suffering—white arrows (magnification 200×). (C) The negative expression of CD14 in a specimen belonging to the control group. The causes of death in the control group were not related to heart disease (magnification 100×). (D) Immunohistochemical image of numerous myocardial fibers with inflammatory cells intercalated, with the membrane marked in brown, showing low CD14 expression (<10%)—white arrows (magnification 40×). (E) Immunohistochemical image of the myocardial cells, with numerous inflammatory cells intercalated and membranous immune expression of CD14 marked in brown and white arrows. Its expression is revealed mainly on the macrophage membrane surface, but also minimally distributed on the neutrophil surface of mCD14. No expression is seen in the blood vessels—yellow arrows (magnification 40×). (F) Immunohistochemical image of a blood vessel located intramuscularly—yellow arrows. In the vessel’s lumen there can be noticed granular areas of extracellular, soluble CD14 (brown color) along with monocytes and neutrophils (mCD14)—white arrows (magnifications 40×). Copyright P. M. Reil, T. T. Maghiar, N. Vîlceanu, A. Pascalau, Claudia Teodora Judea Pusta, F. Marcu , Simona Cavalu and Ovidiu Pop

The study showed: 1) a positive association between markedly increased values of CD14 and an adverse patient evolution; 2) significant increase in the level of membranous and soluble CD14 surface protein in the study group; 3) tendency for higher values in relation to older patients, but without statistical significance; 4) no statistically relevant difference regarding the patient’s gender, provenance, or infection site; 5) a positive association between cellular expression (membranous, mCD14) and intravascular (soluble, sCD14) levels; 6) CD14 plays a double role: (a) as a component of the innate immune system, a pattern recognition receptor (PRR) proposed to bind conserved molecular structures on microbes (pathogen-associated molecular patterns, PAMPs, e.g., LPS); (b) as an active agent involved in the apoptotic cell cleaning process. Apoptotic cell-associated molecular patterns (ACAMPs) interfere with PRR and LPS-like
structures, as revealed on apoptotic cells. (Copyright P. M. Reil, T. T. Maghiar, N. Vîlceanu, A. Pascalau, Claudia Teodora Judea Pusta, F. Marcu , Ovidiu Pop and Simona Cavalu)

We suggest that a large amount of sCD14 detected in the myocardial tissue will activate the mCD14–TRL4–LBP–LPS complex and further induce an inadequate immune response, resulting in severe heart damage. A higher amount of LPS will induce more significant heart damage. Identification of the presence of mCD14 and sCD14 in the myocardium tissue can allow the indubitable diagnosis of septic cardiomyopathy. (Copyright P. M. Reil, T. T. Maghiar, N. Vîlceanu, A. Pascalau, Claudia Teodora Judea Pusta, F. Marcu , Simona Cavalu and Ovidiu Pop)

Full text available at: https://www.mdpi.com/2075-4418/12/4/781/htm