The mannose 6-phosphate/insulin-like growth factor 2 receptor mediates plasminogen-induced efferocytosis

Abstract

The plasminogen system is harnessed in a wide variety of physiological processes, such as fibrinolysis, cell migration, or efferocytosis; and accordingly, it is essential upon inflammation, tissue remodeling, wound healing, and for homeostatic maintenance in general. Previously, we identified a plasminogen receptor in the mannose 6‐phosphate/insulin‐like growth factor 2 receptor (M6P/IGF2R, CD222). Here, we demonstrate by means of genetic knockdown, knockout, and rescue approaches combined with functional studies that M6P/IGF2R is up‐regulated on the surface of macrophages, recognizes plasminogen exposed on the surface of apoptotic cells, and mediates plasminogen‐induced efferocytosis. The level of uptake of plasminogen‐coated apoptotic cells inversely correlates with the TNF‐α production by phagocytes indicating tissue clearance without inflammation by this mechanism. Our results reveal an up‐to‐now undetermined function of M6P/IGF2R in clearance of apoptotic cells, which is crucial for tissue homeostasis.

Analysis of cell-specific peripheral blood biomarkers in severe allergic asthma identifies innate immune dysfunction

“…Volcano plots (Figure 1B) indicate two genes upregulated in asthmatic monocytes compared to healthy controls (IGF2R and C3AR1). IGF2R is upregulated in monocytes during differentiation into macrophages 4 but changes in IGF2R expression by monocytes in asthma have not previously been observed. C3AR1 has been previously identified as a susceptibility gene for bronchial asthma 5 .…”

“…Two genes, IGF2R and C3AR1 were upregulated in monocytes from asthmatics. IGF2R upregulation has been observed in monocytes during differentiation into macrophages 7 and assists in efferocytosis. Changes in IGF2R expression by monocytes in asthma have not previously been observed, although sputum cells show upregulation 2 .…”

Blockade of TMPRSS2-mediated priming of SARS-CoV-2 by lactoferricin

“…Immunoblotting was performed as described previously ( 48 ). Briefly, samples obtained from in vitro proteolysis or binding assays were analyzed by electrophoresis on an 8% SDS-polyacrylamide gel (SDS-PAGE) followed by a transfer at constant voltage (15 V) to an Immobilon polyvinylidene difluoride membrane (Millipore Co., Bedford, MA).…”

Analysis of cell‐specific peripheral blood biomarkers in severe allergic asthma identifies innate immune dysfunction

“…Volcano plots (Figure 1B,C) indicated two genes upregulated in asthmatic monocytes compared to healthy controls (IGF2R and C3AR1). IGF2R is known to be upregulated in monocytes during differentiation into macrophages, 4 but changes in IGF2R expression by monocytes in asthma have not previously been observed. C3AR1 has been previously identified as a susceptibility gene for bronchial asthma 5 .…”