Details

Autor(en) / Beteiligte

• Myung, Peggy S.
• Clements, James L.
• White, Doug W.
• Malik, Zulfiqar A.
• Cowdery, John S.
• Allen, Lee-Ann H.
• Harty, John T.
• Kusner, David J.
• Koretzky, Gary A.

Titel

In vitro and in vivo macrophage function can occur independently of SLP-76

Ist Teil von

• International immunology, 2000-06, Vol.12 (6), p.887-897

Ort / Verlag

England: Oxford University Press

Erscheinungsjahr

2000

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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)-γ following TCR, platelet collagen receptor and mast cell FcϵR 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 FcγR-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 FcγR 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-γ2 following FcγR ligation. Furthermore, SLP-76–/– BMM display normal FcγR-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-γ. 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 FcγR-induced pathways in some cell types, activation of FcγR-dependent pathways occurs independently of SLP-76 in BMM.