The pattern-recognition molecule mindin binds integrin Mac-1 to promote macrophage phagocytosis via Syk activation and NF-κB p65 translocation

J Cell Mol Med. 2019 May;23(5):3402-3416. doi: 10.1111/jcmm.14236. Epub 2019 Mar 14.


Mindin has a broad spectrum of roles in the innate immune system, including in macrophage migration, antigen phagocytosis and cytokine production. Mindin functions as a pattern-recognition molecule for microbial pathogens. However, the underlying mechanisms of mindin-mediated phagocytosis and its exact membrane receptors are not well established. Herein, we generated mindin-deficient mice using the CRISPR-Cas9 system and show that peritoneal macrophages from mindin-deficient mice were severely defective in their ability to phagocytize E coli. Phagocytosis was enhanced when E coli or fluorescent particles were pre-incubated with mindin, indicating that mindin binds directly to bacteria or non-pathogen particles and promotes phagocytosis. We defined that 131 I-labelled mindin binds with integrin Mac-1 (CD11b/CD18), the F-spondin (FS)-fragment of mindin binds with the αM -I domain of Mac-1 and that mindin serves as a novel ligand of Mac-1. Blockade of the αM -I domain of Mac-1 using either a neutralizing antibody or si-Mac-1 efficiently blocked mindin-induced phagocytosis. Furthermore, mindin activated the Syk and MAPK signalling pathways and promoted NF-κB entry into the nucleus. Our data indicate that mindin binds with the integrin Mac-1 to promote macrophage phagocytosis through Syk activation and NF-κB p65 translocation, suggesting that the mindin/Mac-1 axis plays a critical role during innate immune responses.

Keywords: Mac-1; mindin; phagocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Nucleus / metabolism
  • Extracellular Matrix Proteins / metabolism*
  • HEK293 Cells
  • Humans
  • Macrophage-1 Antigen / chemistry
  • Macrophage-1 Antigen / metabolism*
  • Macrophages / cytology*
  • Macrophages / metabolism*
  • Mice
  • Mice, Knockout
  • Phagocytosis*
  • Phosphorylation
  • Protein Binding
  • Protein Domains
  • Protein Transport
  • RAW 264.7 Cells
  • Receptors, Pattern Recognition / metabolism*
  • Syk Kinase / metabolism*
  • Transcription Factor RelA / metabolism*


  • Extracellular Matrix Proteins
  • Macrophage-1 Antigen
  • Receptors, Pattern Recognition
  • Transcription Factor RelA
  • mindin
  • Syk Kinase