The Selective Expansion and Targeted Accumulation of Bone Marrow-Derived Macrophages Drive Cardiac Vasculitis

Area of Science:

• Cardiovascular Biology
• Immunology
• Macrophage Biology

Background:

• The adult heart harbors diverse macrophage populations originating from embryonic and adult bone marrow (BM) precursors.
• Understanding the localization and roles of these distinct macrophage subsets in cardiac health and disease is crucial.

Purpose of the Study:

• To investigate the distinct localization of embryonic and BM-derived cardiac macrophages.
• To determine their relative contributions during cardiac inflammation, specifically in a model of Kawasaki disease.

Main Methods:

• Utilized reciprocal expression of Lyve-1 and Ccr2 to differentiate macrophage origins in mice and humans.
• Analyzed cardiac tissue in a mouse model of Kawasaki disease to observe macrophage dynamics during inflammation.

Main Results:

• Both embryonic (Lyve-pos) and BM-derived (Ccr2-pos) macrophages reside in major cardiac vessels in healthy states.
• Acute inflammation in a Kawasaki disease model led to increased BM-derived macrophages, particularly around cardiac vessels, coinciding with a loss of embryonic macrophages.
• This BM-derived macrophage accumulation is an initial step in developing cardiac vasculitis.
• Ccr2-pos macrophage accumulation and vasculitis development occurred near Ccr2 chemokine ligand-producing epicardial cells.

Conclusions:

• Perivascular accumulation of BM-derived macrophages is pivotal in cardiac vasculitis pathogenesis.
• The epicardium may play a role in directing inflammation to cardiac vessels via chemokine signaling.
• Identified mechanisms governing macrophage recruitment to the heart during inflammation.