Journal article
In vitro and in vivo macrophage function can occur independently of SLP-76
International immunology, Vol.12(6), pp.887-897
06/01/2000
DOI: 10.1093/intimm/12.6.887
PMID: 10837416
Abstract
Expression of SH2 domain-containing leukocyte-specific phosphoprotein of 76 kDa (SLP-76), a hematopoietic cell-specific adapter protein, is required to couple Syk family tyrosine kinase activation to downstream mediators such as phospholipase C (PLC)-gamma following TCR, platelet collagen receptor and mast cell Fc epsilon R stimulation. In addition to T cells, mast cells and platelets, SLP-76 is expressed in monocytes and macrophages. To determine the role of SLP-76 in Fc gamma R-stimulated signaling pathways in macrophages, we examined cultured bone marrow-derived macrophages (BMM) from SLP-76(-/-) and wild-type mice. In this study, we show that Fc gamma R cross-linking rapidly induces tyrosine phosphorylation of SLP-76 in wild-type BMM. Surprisingly, however, BMM from SLP-76(-/-) mice activate ERK2 and phosphorylate PLC-gamma 2 following Fc gamma R ligation. Furthermore, SLP-76(-/-) BMM display normal Fc gamma R-dependent phagocytic function and reactive oxygen intermediate production. SLP-76(-/-) and SLP-76(+/+) BMM secrete comparable levels of IL-12 in response to lipopolysaccharide and IFN-gamma. To examine macrophage function in vivo, SLP-76(-/-) mice were challenged i.v. with Listeria monocytogenes. SLP-76(-/-) mice survive and efficiently contain the acute phase of infection similar to wild-type mice but exhibit a stable chronic infection attributed to the lack of mature T cells. These data show that, although SLP-76 is required to couple Syk family PTK activity to downstream mediators and effector functions in Fc gamma R-induced pathways in some cell types, activation of Fc gamma R-dependent pathways occurs independently of SLP-76 in BM
Details
- Title: Subtitle
- In vitro and in vivo macrophage function can occur independently of SLP-76
- Creators
- Peggy S MyungJames L ClementsDoug W WhiteZulfiqar A MalikJohn S CowderyLee-Ann H AllenJohn T HartyDavid J KusnerGary A Koretzky
- Resource Type
- Journal article
- Publication Details
- International immunology, Vol.12(6), pp.887-897
- DOI
- 10.1093/intimm/12.6.887
- PMID
- 10837416
- ISSN
- 0953-8178
- eISSN
- 1460-2377
- Language
- English
- Date published
- 06/01/2000
- Academic Unit
- Infectious Diseases; Pathology; Immunology; Internal Medicine
- Record Identifier
- 9984047713802771
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