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Adhesion molecule-dependent mechanisms regulate the rate of macrophage clearance during the resolution of peritoneal inflammation

Bellingan, GJ; Xu, P; Cooksley, H; Cauldwell, H; Shock, A; Bottoms, S; Haslett, C; ... Laurent, GJ; + view all (2002) Adhesion molecule-dependent mechanisms regulate the rate of macrophage clearance during the resolution of peritoneal inflammation. J EXP MED , 196 (11) 1515 - 1521. 10.1084/jem.20011794. Green open access

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Abstract

Macrophage clearance is essential for the resolution of inflammation. Much is known about how monocytes enter the inflammatory site but little is known about how resultant macrophages are cleared. We have previously demonstrated that macrophage clearance from resolving peritonitis occurs by emigration into draining lymphatics rather than local apoptosis. We now examine mechanisms for this process, in particular by evaluating the hypothesis that modulation of adhesion interactions between macrophages and cells lining the lymphatics regulates the rate of macrophage clearance. We demonstrate in vivo that macrophages adhere specifically to mesothelium overlying draining lymphatics and that their emigration rate is regulated by the state of macrophage activation. We observed that macrophage-mesothelial adhesion is Arg-Gly-Asp (RGD) sensitive and partially mediated by very late antigen (VLA)-4 and VLA-5 but not alpha(v) or beta2 integrins. Moreover, macrophage clearance into lymphatics can be blocked in vivo by RGD peptides and VLA-4 and VLA-5 but not beta(2) blocking antibodies. This is the first evidence that macrophage emigration from the inflamed site is controlled and demonstrates that this is exerted through specific adhesion molecule regulation of macrophage-mesothelial interactions. It highlights the importance of adhesion molecules governing entry of cells into the lymphatic circulation, thus opening a new avenue for manipulating the resolution of inflammation.

Type: Article
Title: Adhesion molecule-dependent mechanisms regulate the rate of macrophage clearance during the resolution of peritoneal inflammation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1084/jem.20011794
Keywords: peritonitis, integrins, lymphatic systein, cell inovernent, receptors-very late antigen, DRAINING LYMPH-NODES, IN-VIVO, LATE ANTIGEN-4, MILKY SPOTS, CELLS, EXPRESSION, INTEGRINS, APOPTOSIS, INJURY
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Internal Medicine
UCL > Provost and Vice Provost Offices > VP Health
UCL > Provost and Vice Provost Offices > VP Health > Translational Research Office
URI: https://discovery.ucl.ac.uk/id/eprint/8025
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