Ingo Hilgendorf 1 , Louisa M S Gerhardt , Timothy C Tan , Carla Winter , Tobias A W Holderried , Benjamin G Chousterman , Yoshiko Iwamoto , Ronglih Liao , Andreas Zirlik , Marielle Scherer-Crosbie , Catherine C Hedrick , Peter Libby , Matthias Nahrendorf , Ralph Weissleder , Filip K Swirski
May 09 2014
Healing after myocardial infarction involves the biphasic accumulation of inflammatory lymphocyte antigen 6C (Ly-6C)(high) and reparative Ly-6C(low) monocytes/macrophages (Mo/MΦ). According to 1 model, Mo/MΦ heterogeneity in the heart originates in the blood and involves the sequential recruitment of distinct monocyte subsets that differentiate to distinct macrophages. Alternatively, heterogeneity may arise in tissue from 1 circulating subset via local macrophage differentiation and polarization. The orphan nuclear hormone receptor, nuclear receptor subfamily 4, group a, member 1 (Nr4a1), is essential to Ly-6C(low) monocyte production but dispensable to Ly-6C(low) macrophage differentiation; dependence on Nr4a1 can thus discriminate between systemic and local origins of macrophage heterogeneity.