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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F19%3A00507816" target="_blank" >RIV/67985823:_____/19:00507816 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.jbc.org/content/294/19/7833" target="_blank" >https://www.jbc.org/content/294/19/7833</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1074/jbc.RA118.006314" target="_blank" >10.1074/jbc.RA118.006314</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

—

Svazek periodika

294

Číslo periodika v rámci svazku

19

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

7833-7849

Kód UT WoS článku

000470153300025

EID výsledku v databázi Scopus

2-s2.0-85066002918