Interaction between the integrin Mac-1 and signal regulatory protein (SIRP) mediates fusion in heterologous cells

0507816 - FGÚ 2020 RIV US eng J - Článek v odborném periodiku
Podolnikova, N. P. - Hlaváčková, Markéta - Wu, Y. - Yakubenko, V. P. - Faust, J. - Balabiyev, A. - Wang, X. - Ugarova, T. P.
Interaction between the integrin Mac-1 and signal regulatory protein (SIRP) mediates fusion in heterologous cells.
Journal of Biological Chemistry. Roč. 294, č. 19 (2019), s. 7833-7849. ISSN 0021-9258. E-ISSN 1083-351X
Institucionální podpora: RVO:67985823
Klíčová slova: integrin * cell adhesion * cell-cell interaction * structure-function * macrophage * cell-cell fusion * chronic inflammation
Obor OECD: Physiology (including cytology)
Impakt faktor: 4.238, rok: 2019
Způsob publikování: Open access s časovým embargem
https://www.jbc.org/content/294/19/7833

Macrophage fusion leading to the formation of multinucleated giant cells is a hallmark of chronic inflammation. Several membrane proteins have been implicated in mediating cell-cell attachment during fusion, but their binding partners remain unknown. Recently, we demonstrated that interleukin-4 (IL-4)-induced fusion of mouse macrophages depends on the integrin macrophage antigen 1 (Mac-1). Surprisingly, the genetic deficiency of intercellular adhesion molecule 1 (ICAM-1), an established ligand of Mac-1, did not impair macrophage fusion, suggesting the involvement of other counter-receptors. Here, using various approaches, including signal regulatory protein (SIRP) knockdown, recombinant proteins, adhesion and fusion assays, biolayer interferometry, and peptide libraries, we show that SIRP, which, similar to ICAM-1, belongs to the Ig superfamily and has previously been implicated in cell fusion, interacts with Mac-1. The following results support the conclusion that SIRP is a ligand of Mac-1: (a) recombinant ectodomain of SIRP supports adhesion of Mac-1-expressing cells, (b) Mac-1-SIRP interaction is mediated through the ligand-binding I-M-domain of Mac-1, (c) recognition of SIRP by the I-M-domain conforms to general principles governing binding of Mac-1 to many of its ligands, (d) SIRP reportedly binds CD47, however, anti-CD47 function-blocking mAb produced only a limited inhibition of macrophage adhesion to SIRP, and (e) co-culturing of SIRP- and Mac-1-expressing HEK293 cells resulted in the formation of multinucleated cells. Taken together, these results identify SIRP as a counter-receptor for Mac-1 and suggest that the Mac-1-SIRP interaction may be involved in macrophage fusion.
Trvalý link: http://hdl.handle.net/11104/0298783