Intimal macrophages develop from circulating monocytes during vasculitis
Abstract Objective Vasculitis is characterised by inflammation of the blood vessels. While all layers of the vessel can be affected, inflammation within the intimal layer can trigger thrombosis and arterial occlusion and is therefore of particular clinical concern. Given this pathological role, we h...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Clinical & Translational Immunology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cti2.1412 |
| _version_ | 1817996103286521856 |
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| author | Angus T Stock Sarah Parsons Varun J Sharma Fiona James Graham Starkey Rohit D'Costa Claire L Gordon Ian P Wicks |
| author_facet | Angus T Stock Sarah Parsons Varun J Sharma Fiona James Graham Starkey Rohit D'Costa Claire L Gordon Ian P Wicks |
| author_sort | Angus T Stock |
| collection | DOAJ |
| description | Abstract Objective Vasculitis is characterised by inflammation of the blood vessels. While all layers of the vessel can be affected, inflammation within the intimal layer can trigger thrombosis and arterial occlusion and is therefore of particular clinical concern. Given this pathological role, we have examined how intimal inflammation develops by exploring which (and how) macrophages come to populate this normally immune‐privileged site during vasculitis. Methods We have addressed this question for Kawasaki disease (KD), which is a type of vasculitis in children that typically involves the coronary arteries. We used confocal microscopy and flow cytometry to characterise the macrophages that populate the coronary artery intima in KD patient samples and in a mouse model of KD, and furthermore, have applied an adoptive transfer system to trace how these intimal macrophages develop. Results In KD patients, intimal hyperplasia coincided with marked macrophage infiltration of the coronary artery intima. Phenotypic analysis revealed that these ‘intimal macrophages’ did not express markers of resident cardiac macrophages, such as Lyve‐1, and instead, were uniformly positive for the chemokine receptor Ccr2, suggesting a monocytic lineage. In support of this origin, we show that circulating monocytes directly invade the intima via transluminal migration during established disease, coinciding with the activation of endothelial cells lining the coronary arteries. Conclusions During KD, intimal macrophages develop from circulating monocytes that infiltrate the inflamed coronary artery intima by transluminal migration. |
| first_indexed | 2024-04-14T02:17:11Z |
| format | Article |
| id | doaj.art-00146f0bc9ee44c0a58cebd9e6f139af |
| institution | Directory Open Access Journal |
| issn | 2050-0068 |
| language | English |
| last_indexed | 2024-04-14T02:17:11Z |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical & Translational Immunology |
| spelling | doaj.art-00146f0bc9ee44c0a58cebd9e6f139af2022-12-22T02:18:08ZengWileyClinical & Translational Immunology2050-00682022-01-01118n/an/a10.1002/cti2.1412Intimal macrophages develop from circulating monocytes during vasculitisAngus T Stock0Sarah Parsons1Varun J Sharma2Fiona James3Graham Starkey4Rohit D'Costa5Claire L Gordon6Ian P Wicks7Walter and Eliza Hall Institute of Medical Research Parkville VIC AustraliaDepartment of Forensic Medicine Monash University Melbourne VIC AustraliaLiver & Intestinal Transplant Unit Austin Health Melbourne VIC AustraliaDepartment of Infectious Diseases Austin Health Melbourne VIC AustraliaLiver & Intestinal Transplant Unit Austin Health Melbourne VIC AustraliaDonateLife Victoria Carlton VIC AustraliaDepartment of Infectious Diseases Austin Health Melbourne VIC AustraliaWalter and Eliza Hall Institute of Medical Research Parkville VIC AustraliaAbstract Objective Vasculitis is characterised by inflammation of the blood vessels. While all layers of the vessel can be affected, inflammation within the intimal layer can trigger thrombosis and arterial occlusion and is therefore of particular clinical concern. Given this pathological role, we have examined how intimal inflammation develops by exploring which (and how) macrophages come to populate this normally immune‐privileged site during vasculitis. Methods We have addressed this question for Kawasaki disease (KD), which is a type of vasculitis in children that typically involves the coronary arteries. We used confocal microscopy and flow cytometry to characterise the macrophages that populate the coronary artery intima in KD patient samples and in a mouse model of KD, and furthermore, have applied an adoptive transfer system to trace how these intimal macrophages develop. Results In KD patients, intimal hyperplasia coincided with marked macrophage infiltration of the coronary artery intima. Phenotypic analysis revealed that these ‘intimal macrophages’ did not express markers of resident cardiac macrophages, such as Lyve‐1, and instead, were uniformly positive for the chemokine receptor Ccr2, suggesting a monocytic lineage. In support of this origin, we show that circulating monocytes directly invade the intima via transluminal migration during established disease, coinciding with the activation of endothelial cells lining the coronary arteries. Conclusions During KD, intimal macrophages develop from circulating monocytes that infiltrate the inflamed coronary artery intima by transluminal migration.https://doi.org/10.1002/cti2.1412intimal hyperplasiaKawasaki diseasemacrophagesmonocytesvasculitis |
| spellingShingle | Angus T Stock Sarah Parsons Varun J Sharma Fiona James Graham Starkey Rohit D'Costa Claire L Gordon Ian P Wicks Intimal macrophages develop from circulating monocytes during vasculitis Clinical & Translational Immunology intimal hyperplasia Kawasaki disease macrophages monocytes vasculitis |
| title | Intimal macrophages develop from circulating monocytes during vasculitis |
| title_full | Intimal macrophages develop from circulating monocytes during vasculitis |
| title_fullStr | Intimal macrophages develop from circulating monocytes during vasculitis |
| title_full_unstemmed | Intimal macrophages develop from circulating monocytes during vasculitis |
| title_short | Intimal macrophages develop from circulating monocytes during vasculitis |
| title_sort | intimal macrophages develop from circulating monocytes during vasculitis |
| topic | intimal hyperplasia Kawasaki disease macrophages monocytes vasculitis |
| url | https://doi.org/10.1002/cti2.1412 |
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