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Published online before print December 23, 2003
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receptor-mediated signaling do not require expression of the SLP-76 and SLP-65 adaptors
,1
,¶
* Pediatric Oncology, Children’s Hospital of Philadelphia, Pennsylvania;
Abramson Family Cancer Research Institute and Departments of
Microbiology and
¶ Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia; and
Max Planck Institute for Immunobiology, Freiburg, Germany
1 Correspondence: Children’s Hospital of Philadelphia, Pediatric Oncology, ARC 907C, 3615 Civic Center Boulevard, Philadelphia, PA 19104. E-mail: nicholsk{at}email.chop.edu
The Src-homology 2 domain-containing, leukocyte-specific phosphoprotein of 76 kDa (SLP-76) is a hematopoietic adaptor that plays a central role during immunoreceptor-mediated activation of T lymphocytes and mast cells and collagen receptor-induced activation of platelets. Despite similar levels of expression in macrophages, SLP-76 is not required for Fc receptor for immunoglobulin G (IgG; Fc
R)-mediated activation. We hypothesized that the related adaptor SLP-65, which is also expressed in macrophages, may compensate for the loss of SLP-76 during FcR-mediated signaling and functional events. To address this hypothesis, we examined bone marrow-derived macrophages (BMM) from wild-type (WT) mice or mice lacking both of these adaptors. Contrary to our expectations, SLP-76-/- SLP-65-/- BMM demonstrated normal FcR-mediated activation, including internalization of Ig-coated sheep red blood cells and production of reactive oxygen intermediates. FcR-induced biochemical events were normal in SLP-76-/- SLP-65-/- BMM, including phosphorylation of phospholipase C and the extracellular signaling-regulated kinases 1 and 2. To determine whether macrophages functioned normally in vivo, we infected WT and SLP-76-/- SLP-65-/- mice with sublethal doses of Listeria monocytogenes (LM), a bacterium against which the initial host defense is provided by activated macrophages. WT and SLP-76-/- SLP-65-/- mice survived acute, low-dose infection and showed no difference in the number of liver or spleen LM colony-forming units, a measure of the total body burden of this organism. Taken together, these data suggest that neither SLP-76 nor SLP-65 is required during FcR-dependent signaling and functional events in macrophages.
Key Words: innate immunity • phagocytosis • ITAM • respiratory burst
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