Functional association of CD9 with the Fcγ receptors in macrophages

K. Kaji, S. Takeshita, K. Miyake, T. Takai, A. Kudo

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

Abstract

CD9, a member of the tetraspan family of proteins, is highly expressed on macrophages. Although a clear function for the molecule has yet to be described, we have found that the anti-CD9 mAb activates mouse macrophages. The rat anti-CD9 mAb, KMC8.8, but not the F(ab′)2, induced tyrosine phosphorylation of proteins including syk and cbl and induced cell aggregation in the mouse macrophage cell line, J774, suggesting that co-cross-linking of CD9 and FcγR was required for the signal. Co-cross-linking of CD9-FcγR with KMC8.8 on macrophages from three different FcR-deficient mice, FcR γ-chain-/-, FcγRIIB-/-, and FcγRIII-/-, revealed that FcγRIII is specific and crucial for syk phosphorylation. Although both KMC8.8 and the anti-FcγRIIB/III mAb, 2.4G2, evoked similar phosphorylation patterns, only KMC8.8 induced cell aggregation. Additionally, KMC8.8 treatment led to reduce levels of TNF-α production and p42/44 extracellular signal-related kinase phosphorylation relative to 2.4G2 stimulation. Immunofluorescence staining showed that co-cross-linking of CD9-FcγR with KMC8.8 induced filopodium extension before cell aggregation, which was followed by simultaneous colocalization of CD9, FcγRIIB/III, Mac-1, ICAM-1, and F-actin at the cell-cell adhesion site. Moreover, KMC8.8 treatment of FcγR-deficient macrophages revealed that the colocalization of CD9, FcγRIII, Mac-1, and F-actin requires co-cross-linking of CD9-FcγRIII, whereas co-cross-linking of CD9-FcγRIIB induced the colocalization of only CD9 and FcγRIIB. Our results demonstrate that co-cross-linking of CD9 and FcγRs activates macrophages; therefore, CD9 may collaborate with FcRs functioning in infection and inflammation on macrophages.

Original languageEnglish
Pages (from-to)3256-3265
Number of pages10
JournalJournal of Immunology
Volume166
Issue number5
DOIs
Publication statusPublished - 2001 Mar 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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