The mast cell tumor necrosis factor alpha response to FimH-expressing Escherichia coli is mediated by the glycosylphosphatidylinositol-anchored molecule CD48.

Journal Article (Journal Article)

Mast cells are well known for their harmful role in IgE-mediated hypersensitivity reactions, but their physiological role remains a mystery. Several recent studies have reported that mast cells play a critical role in innate immunity in mice by releasing tumor necrosis factor alpha (TNF-alpha) to recruit neutrophils to sites of enterobacterial infection. In some cases, the mast cell TNF-alpha response was triggered when these cells directly bound FimH on the surface of Escherichia coli. We have identified CD48, a glycosylphosphatidylinositol-anchored molecule, to be the complementary FimH-binding moiety in rodent mast cell membrane fractions. We showed that (i) pretreatment of mast cell membranes with antibodies to CD48 or phospholipase C inhibited binding of FimH+ E. coli, (ii) FimH+ E. coli but not a FimH- derivative bound isolated CD48 in a mannose-inhibitable manner, (iii) binding of FimH+ bacteria to Chinese hamster ovary (CHO) cells was markedly increased when these cells were transfected with CD48 cDNA, and (iv) antibodies to CD48 specifically blocked the mast cell TNF-alpha response to FimH+ E. coli. Thus, CD48 is a functionally relevant microbial receptor on mast cells that plays a role in triggering inflammation.

Full Text

Duke Authors

Cited Authors

  • Malaviya, R; Gao, Z; Thankavel, K; van der Merwe, PA; Abraham, SN

Published Date

  • July 6, 1999

Published In

Volume / Issue

  • 96 / 14

Start / End Page

  • 8110 - 8115

PubMed ID

  • 10393956

Pubmed Central ID

  • PMC22196

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.96.14.8110


  • eng

Conference Location

  • United States