Lack of Neutrophil-Derived CRAMP Reduces Atherosclerosis in Mice

• Published in: Circulation research Vol. 110; no. 8; pp. 1052 - 1056
• Main Authors: Döring, Yvonne, Drechsler, Maik, Wantha, Sarawuth, Kemmerich, Klaus, Lievens, Dirk, Vijayan, Santosh, Gallo, Richard L, Weber, Christian, Soehnlein, Oliver
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 13.04.2012; Lippincott Williams & Wilkins
• Subjects: Animals; Antimicrobial Cationic Peptides; Aorta; Aorta - immunology; Aorta - metabolism; Aorta - pathology; Aortic Diseases - genetics; Aortic Diseases - immunology; Aortic Diseases - metabolism; Aortic Diseases - pathology; Aortic Diseases - prevention & control; Apolipoproteins E - deficiency; Apolipoproteins E - genetics; Arteries; Arteriosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - genetics; Atherosclerosis - immunology; Atherosclerosis - metabolism; Atherosclerosis - pathology; Atherosclerosis - prevention & control; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; cathelicidins; Cathelicidins - deficiency; Cathelicidins - genetics; Cell Adhesion; Cells, Cultured; Chemotaxis, Leukocyte; Coculture Techniques; Disease Models, Animal; Endothelium; Endothelium, Vascular - immunology; Endothelium, Vascular - metabolism; formyl peptides; Fundamental and applied biological sciences. Psychology; Granules; Humans; Inflammation; Inflammation - genetics; Inflammation - immunology; Inflammation - metabolism; Inflammation - pathology; Inflammation - prevention & control; Leukocytes (neutrophilic); Macrophages; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy; Microscopy, Fluorescence; Monocytes; Monocytes - immunology; Monocytes - metabolism; Neutrophils - immunology; Neutrophils - metabolism; Time Factors; Vertebrates: cardiovascular system; Monocyte; Rodentia; Cardiovascular disease; monocyte recruitment; Recruitment; Vascular disease; Cramp; Striated muscle disease; Vertebrata; Mammalia; Mouse; Atherosclerosis; Circulatory system; Neutrophil
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/CIRCRESAHA.112.265868

RATIONALE:Neutrophils have been reported to contribute to early atherosclerotic lesion formation. Mechanisms of neutrophil-driven atherosclerosis remain unclear so far. OBJECTIVE:Investigation of the role of the neutrophil granule protein cathelicidin (CRAMP in mouse, LL37 in human) in atherosclerosis. METHODS AND RESULTS:Compared to Apoe mice, Cramp Apoe mice exhibit reduced lesion sizes with lower macrophage numbers. In atherosclerotic aortas, we could detect CRAMP specifically in neutrophils, but not in monocytes or macrophages. By use of intravital microscopy, CRAMP was found to be deposited by activated neutrophils on inflamed endothelium of large arteries. In this location cathelicidins promote adhesion of classical monocytes and neutrophils, but not nonclassical monocytes in a formyl-peptide receptor-dependent manner. CONCLUSIONS:Cathelicidins promote atherosclerosis by enhancement of the recruitment of inflammatory monocytes.