Fcγ Receptor–Mediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn

Fitzer‐Attas, Cheryl; Lowry, Malcolm B.; Crowley, Mary T.; Finn, Alexander J.; Meng, Fanying; DeFranco, Anthony L.; Lowell, Clifford A.

doi:10.1084/jem.191.4.669

Cited by 238 publications

(211 citation statements)

References 50 publications

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“…Among these signal transduction pathway components, Src family kinases, Syk kinase and the adapter protein LAT have all been shown to play critical roles in Fc␥R-regulated phagocytosis (75,(77)(78)(79). In addition, FcR-mediated phagocytosis is via Ca 2ϩ -dependent and Ca 2ϩ -independent pathways (80 -83) Moreover, PKC, which is activated by PLC␥, has been reported to play a role in regulating phagocytosis (83,84).…”

Section: Discussionmentioning

confidence: 99%

Phospholipase Cγ2 Is Essential for Specific Functions of FcεR and FcγR

Wen

Jou

Chen

et al. 2002

The Journal of Immunology

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Phospholipase Cγ2 (PLCγ2) plays a critical role in the functions of the B cell receptor in B cells and of the FcRγ chain-containing collagen receptor in platelets. Here we report that PLCγ2 is also expressed in mast cells and monocytes/macrophages and is activated by cross-linking of FcεR and FcγR. Although PLCγ2-deficient mice have normal development and numbers of mast cells and monocytes/macrophages, we demonstrate that PLCγ2 is essential for specific functions of FcεR and FcγR. While PLCγ2-deficient mast cells have normal mitogen-activated protein kinase activation and cytokine production at mRNA levels, the mutant cells have impaired FcεR-mediated Ca2+ flux and inositol 1,4,5-trisphosphate production, degranulation, and cytokine secretion. As a physiological consequence of the effect of PLCγ2 deficiency, the mutant mice are resistant to IgE-mediated cutaneous inflammatory skin reaction. Macrophages from PLCγ2-deficient mice have no detectable FcγR-mediated Ca2+ flux; however, the mutant cells have normal FcγR-mediated phagocytosis. Moreover, PLCγ2 plays a nonredundant role in FcγR-mediated inflammatory skin reaction.

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Section: Discussionmentioning

confidence: 99%

Phospholipase Cγ2 Is Essential for Specific Functions of FcεR and FcγR

Wen

Jou

Chen

et al. 2002

The Journal of Immunology

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“…208 Triple knockout (hck À/À lyn À/À fgr À/À ) mice (HLF mice) are remarkable for being relatively healthy with normal responses to lipopolysaccharide stimulation and normal phagocytic functions. 209,210 However, HLF mice manifest enhanced neutrophil responses to G-CSF. 202 In addition, HLF mice have increased levels of bone marrow progenitors and show a hyperproliferative response to G-CSF in vitro.…”

Section: Signal Transduction In Myeloid Differentiationmentioning

confidence: 99%

Signal transduction pathways that contribute to myeloid differentiation

Miranda

Johnson

2007

Leukemia

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The production of mature, differentiated myeloid cells is regulated by the action of hematopoietic cytokines on progenitor cells in the bone marrow. Cytokines drive the process of myeloid differentiation by binding to specific cell-surface receptors in a stage-and lineage-specific manner. Following the binding of a cytokine to its cognate receptor, intracellular signal-transduction pathways become activated that facilitate the myeloid differentiation process. These intracellular signaling pathways may promote myelopoiesis by stimulating expansion of a progenitor pool, supporting cellular survival during the differentiation process, or by directly driving the phenotypic changes associated with differentiation. Ultimately, pathways that drive the differentiation process converge on myeloid transcription factors, including PU.1 and the C/EBP family, that are critical for differentiation to proceed. While much is known about the cytokines, cytokine receptors and transcription factors that regulate myeloid differentiation, less is known about the precise roles that specific signaling mediators play in promoting myeloid differentiation. Recently, however, the application of novel pharmacologic inhibitors, siRNA strategies, and transgenic and knockout models has begun to shed light on the involvement and function of signaling pathways in normal myeloid differentiation. This review will discuss the roles that key signaling pathways and mediators play in myeloid differentiation.

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“…In addition, members of the WASP molecular family [25] and of ARF family of GTPases [26] have been involved in ingestion process regulation. The recruitment of src and syk tyrosine kinases by the Fc receptor ITAM motifs [27,28], the generation of 3 0 -phosphoinositides and of phosphatidylinositol-4,5 bisphosphate (PIP2) by PI3K [29,30], the activation of PLC and protein kinase C (PKC) [31], of PKA [32], PLA2 [33], and PLD [34] have also been described in phagocytosis processes. Notably, the needing of PKC-dependent bchain phosphorylation for CR3 and CR4 integrin activation has been demonstrated [35,36].…”

Section: Introductionmentioning

confidence: 99%

Glycosyl‐phosphatidyl‐inositol‐defective granulocytes from paroxysmal nocturnal haemoglobinuria patients show increased bacterial ingestion but reduced respiratory burst induction

et al. 2006

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Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the emergence of a GPI-defective clonal hematopoiesis. Its clinical features are hemolytic anemia, cytopenia, and thrombosis. Circulating monocytes and granulocytes are largely GPI-defective in PNH patients. This study aims to investigate the granulocyte functional properties in PNH. We analyzed bacterial-dependent intracellular ingestion and the consequent activation of oxidative burst in GPI-defective granulocytes from four neutropenic PNH patients. Our data show a significant increase in the ability of GPI-defective granulocytes to ingest opsonized bacteria. In addition, an impaired respiratory burst effectiveness in response to two independent bacterial stimuli, the N-formyl-MetLeuPhe (fMLP) synthetic bacterial peptide and E. coli, was revealed. The occurrence of neutropenia and the severe impairment of oxidative burst, occurring in chronic granulomatosis disease, were unable to significantly affect phagocytosis. Thus, additional mechanisms, able to differentially affect ingestion ability and respiratory burst effectiveness, have to be hypothesized. The reduced burst effectiveness of GPIdefective granulocytes was maintained after treatment with phorbol 12-myristate 13-acetate, a pharmacological stimulus able to extensively recruit and to trigger intracellular protein kinase C (PKC). Moreover, blocking of PKC has been observed to severely affect granulocyte respiratory burst with a mild effect on the phagocytosis. These data suggest a role for a modulation of intracellular PKC in the pathogenesis of the impaired granulocyte oxidative burst. Am. J. Hematol. 82:98-107, 2007. V V C 2006 Wiley-Liss, Inc.

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Fcγ Receptor–Mediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn

Cited by 238 publications

References 50 publications

Phospholipase Cγ2 Is Essential for Specific Functions of FcεR and FcγR

Phospholipase Cγ2 Is Essential for Specific Functions of FcεR and FcγR

Signal transduction pathways that contribute to myeloid differentiation

Glycosyl‐phosphatidyl‐inositol‐defective granulocytes from paroxysmal nocturnal haemoglobinuria patients show increased bacterial ingestion but reduced respiratory burst induction

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