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Differential expression of Plg-R KT and its effects on migration of proinflammatory monocyte and macrophage subsets
Ist Teil von
Blood, 2019-08, Vol.134 (6), p.561
Ort / Verlag
United States
Erscheinungsjahr
2019
Quelle
MEDLINE
Beschreibungen/Notizen
Membrane-bound plasmin is used by immune cells to degrade extracellular matrices, which facilitates migration. The plasminogen receptor Plg-R
is expressed by immune cells, including monocytes and macrophages. Among monocytes and macrophages, distinct subsets can be distinguished based on cell surface markers and pathophysiological function. We investigated expression of Plg-R
by monocyte and macrophage subsets and whether potential differential expression might have functional consequences for cell migration. Proinflammatory CD14
CD16
human monocytes and Ly6C
mouse monocytes expressed the highest levels of Plg-R
and bound significantly more plasminogen compared with the other respective subsets. Proinflammatory human macrophages, generated by polarization with lipopolysaccharide and interferon-γ, showed significantly higher expression of Plg-R
compared with alternatively activated macrophages, polarized with interleukin-4 and interleukin-13. Directional migration of proinflammatory monocytes was plasmin dependent and was abolished by anti-Plg-R
monoclonal antibody, ε-amino-caproic acid, aprotinin, and the aminoterminal fragment of urokinase-type plasminogen activator. In an in vivo peritonitis model, significantly less Ly6C
monocyte recruitment was observed in Plg-R
compared with Plg-R
mice. Immunohistochemical analysis of human carotid plaques and adipose tissue showed that proinflammatory macrophages also exhibited high levels of Plg-R
in vivo. Our data demonstrate higher expression of Plg-R
on proinflammatory monocyte and macrophage subsets that impacts their migratory capacity.