Histamine deficiency facilitates coronary microthrombosis after myocardial infarction by increasing neutrophil-platelet interactions.

Abstract

Neutrophil-platelet interactions are responsible for thrombosis as well as inflammatory responses following acute myocardial infarction (AMI). While histamine has been shown to play a crucial role in many physiological and pathological processes, its effects on neutrophil-platelet interactions in thromboinflammatory complications of AMI remain elusive. In this study, we show a previously unknown mechanism by which neutrophil-derived histamine protects the infarcted heart from excessive neutrophil-platelet interactions and redundant arterial thrombosis. Using histamine-deficient (histidine decarboxylase knockout, HDC-/- ) and wild-type murine AMI models, we demonstrate that histamine deficiency increases the number of microthrombosis after AMI, in accordance with depressed cardiac function. Histamine-producing myeloid cells, mainly Ly6G+ neutrophils, directly participate in arteriole thrombosis. Histamine deficiency elevates platelet activation and aggregation by enhancing Akt phosphorylation and leads to dysfunctional characteristics in neutrophils which was confirmed by high levels of reactive oxygen species production and CD11b expression. Furthermore, HDC-/- platelets were shown to elicit neutrophil extracellular nucleosomes release, provoke neutrophil-platelet interactions and promote HDC-expressing neutrophils recruitment in arteriole thrombosis in vivo. In conclusion, we provide evidence that histamine deficiency promotes coronary microthrombosis and deteriorates cardiac function post-AMI, which is associated with the enhanced platelets/neutrophils function and neutrophil-platelet interactions.

• Authors: Hui Li, Chao Tang, Xiaowei Zhu, Weiwei Zhang, Mieradilijiang Abudupataer, Suling Ding, Caiwen Duan, Xiangdong Yang, Junbo Ge
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 6 Pg. 3504-3520 (03 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 32064748 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Receptors, Histamine
• Histamine
• Proto-Oncogene Proteins c-akt
• Histidine Decarboxylase

Topics

• Animals
• Blood Platelets (drug effects, pathology)
• Cell Communication (drug effects)
• Coronary Vessels (drug effects, pathology)
• Histamine (deficiency, pharmacology)
• Histidine Decarboxylase (deficiency)
• Mice
• Models, Biological
• Myocardial Infarction (complications, pathology)
• Myocardium (pathology)
• Neutrophil Infiltration (drug effects)
• Neutrophils (drug effects, pathology)
• Phosphorylation (drug effects)
• Platelet Aggregation (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Receptors, Histamine (metabolism)
• Thrombopoiesis (drug effects)
• Thrombosis (etiology, pathology)