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Hematopoietic α7 nicotinic acetylcholine receptor deficiency increases inflammation and platelet activation status, but does not aggravate atherosclerosis
Author(s) -
Kooijman S.,
Meurs I.,
Stoep M.,
Habets K. L.,
Lammers B.,
Berbée J. F. P.,
Havekes L. M.,
Eck M.,
Romijn J. A.,
Korporaal S. J. A.,
Rensen P. C. N.
Publication year - 2015
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12765
Subject(s) - inflammation , platelet activation , platelet , acetylcholine receptor , acetylcholine , haematopoiesis , nicotinic agonist , medicine , nicotinic acetylcholine receptor , receptor , biology , microbiology and biotechnology , stem cell
Summary Background The autonomic nervous system attenuates inflammation through activation of the α7 nicotinic acetylcholine receptor (α7n AChR ), a pathway termed the cholinergic anti‐inflammatory reflex. Interestingly, α7n AChR is expressed on immune cells and platelets, both of which play a crucial role in the development of atherosclerosis. Objective To investigate the role of hematopoietic α7n AChR in inflammation and platelet function in atherosclerotic ldlr − / − mice and to identify its consequences for atherosclerotic lesion development. Methods Bone marrow from α 7n AChR − / − mice or wild‐type littermates was transplanted into irradiated ldlr − / − mice. After a recovery period of 8 weeks, the mice were fed an atherogenic Western‐type diet for 7 weeks. Results Hematopoietic α7n AChR deficiency clearly increased the number of leukocytes in the peritoneum (2.6‐fold, P < 0.001), blood (2.9‐fold; P < 0.01), mesenteric lymph nodes (2.0‐fold; P < 0.001) and spleen (2.2‐fold; P < 0.01), indicative of an increased inflammatory status. Additionally, expression of inflammatory mediators was increased in peritoneal leukocytes ( TNF α, 1.6‐fold, P < 0.01; CRP , 1.8‐fold, P < 0.01) as well as in the spleen ( TNF α, 1.6‐fold, P < 0.01). The lack of α7n AChR on platelets from these mice increased the expression of active integrin α IIb β 3 upon stimulation by ADP (1.9‐fold, P < 0.01), indicating increased activation status, while incubation of human platelets with an α7n AChR agonist decreased aggregation (−35%, P < 0.05). Despite the large effects of hematopoietic α7n AChR deficiency on inflammatory status and platelet function, it did not affect atherosclerosis development or composition of lesions. Conclusions Hematopoietic α7n AChR is important for attenuation of inflammatory responses and maintaining normal platelet reactivity, but loss of hematopoietic α7n AChR does not aggravate development of atherosclerosis.