Fcγ-receptors Induce Mac-1 (CD11b/CD18) Mobilization and Accumulation in the Phagocytic Cup for Optimal Phagocytosis

Jongstra‐Bilen, Jenny; Harrison, Rene E.; Grinstein, Sergio

doi:10.1074/jbc.m303704200

Cited by 110 publications

(118 citation statements)

References 54 publications

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“…31 Also, binding of IgG to FcγR increased CR3 function on the mouse macrophage cell line RAW264.7 by inducing the lateral movement of CR3 to FcγR-containing phagocytic cups, enhancing iC3b binding. 32 Although it is clear that cross talk occurs between both receptors, the underlying mechanisms remain largely unclear.…”

Section: Integrin Regulation and Neutrophil Adhesion Migration And mentioning

confidence: 99%

Neutrophil integrin affinity regulation in adhesion, migration, and bacterial clearance

Langereis

2013

Cell Adhesion & Migration

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Section: Integrin Regulation and Neutrophil Adhesion Migration And mentioning

confidence: 99%

Neutrophil integrin affinity regulation in adhesion, migration, and bacterial clearance

Langereis

2013

Cell Adhesion & Migration

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“…In mammalian phagocytes, they may contribute to phagocytosis by mediating the activation of integrins, as shown in lymphoid cells (60,61). Indeed, stimulation of Fc␥R in macrophages activates the complement receptor CR3, an integrin, and this response involves PLC (32). Strikingly, in cells stimulated by IgG-opsonized RBCs, we detected activation of Rap1 by a process that required PLC activity and DAG.…”

Section: Discussionmentioning

confidence: 65%

“…To determine phagosome maturation in the presence of H-RasN17, cells were induced to internalize RBCs, and the phagosomes were allowed to mature for 60 min, followed by fixation and immunostaining for LAMP1. C3bi opsonization and binding assays were performed as described previously (32).…”

Section: Methodsmentioning

confidence: 99%

“…Rap1 regulates phagocytosis in Dictyo- stelium (44) and is required for complement receptor-mediated phagocytosis (45). We previously demonstrated that engagement of Fc␥R cross-activates the complement receptor, CR3, a member of the integrin family, enabling cells to recognize and bind complement-opsonized particles (32). Moreover, this cross-activation requires a DAG-dependent signaling pathway (32).…”

Section: Rap1 Gtpase Is Activated By Diacylglycerol and Modulates Cromentioning

confidence: 99%

“…We previously demonstrated that engagement of Fc␥R cross-activates the complement receptor, CR3, a member of the integrin family, enabling cells to recognize and bind complement-opsonized particles (32). Moreover, this cross-activation requires a DAG-dependent signaling pathway (32). Therefore, we speculated that Rap1 may control Fc␥R-mediated cross-activation of CR3 receptors in a DAG-dependent manner.…”

Section: Rap1 Gtpase Is Activated By Diacylglycerol and Modulates Cromentioning

confidence: 99%

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Localized Diacylglycerol-dependent Stimulation of Ras and Rap1 during Phagocytosis

Botelho

Harrison

Stone

et al. 2009

Journal of Biological Chemistry

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We describe a role for diacylglycerol in the activation of Ras and Rap1 at the phagosomal membrane. During phagocytosis, Ras density was similar on the surface and invaginating areas of the membrane, but activation was detectable only in the latter and in sealed phagosomes. Ras activation was associated with the recruitment of RasGRP3, a diacylglycerol-dependent Ras/ Rap1 exchange factor. Recruitment to phagosomes of RasGRP3, which contains a C1 domain, parallels and appears to be due to the formation of diacylglycerol. Accordingly, Ras and Rap1 activation was precluded by antagonists of phospholipase C and of diacylglycerol binding. Ras is dispensable for phagocytosis but controls activation of extracellular signal-regulated kinase, which is partially impeded by diacylglycerol inhibitors. By contrast, cross-activation of complement receptors by stimulation of Fc␥ receptors requires Rap1 and involves diacylglycerol. We suggest a role for diacylglycerol-dependent exchange factors in the activation of Ras and Rap1, which govern distinct processes induced by Fc␥ receptor-mediated phagocytosis to enhance the innate immune response.Receptors that interact with the constant region of IgG (Fc␥R) 4 mediate the recognition and elimination of soluble immune complexes and particles coated (opsonized) with immunoglobulins. Clustering of Fc␥R on the surface of leukocytes upon attachment to multivalent ligands induces their activation and subsequent internalization. Soluble immune complexes are internalized by endocytosis, a clathrin-and ubiquitylation-dependent process (1). In contrast, large, particulate complexes like IgG-coated pathogens are ingested by phagocytosis, a process that is contingent on extensive actin polymerization that drives the extension of pseudopods (2). In parallel with the internalization of the opsonized targets, crosslinking of phagocytic receptors triggers a variety of other responses that are essential components of the innate immune response. These include degranulation, activation of the respiratory burst, and the synthesis and release of multiple inflammatory agents (3, 4).Like T and B cell receptors, Fc␥R possesses an immunoreceptor tyrosine-based activation motif that is critical for signal transduction (3, 4). Upon receptor clustering, tyrosyl residues of the immunoreceptor tyrosine-based activation motif are phosphorylated by Src family kinases, thereby generating a docking site for Syk, a tyrosine kinase of the ZAP70 family (3, 4). The recruitment and activation of Syk in turn initiates a cascade of events that include activation of Tec family kinases, Rho-and ARF-family GTPases, phosphatidylinositol 3-kinase, phospholipase C␥ (PLC␥), and a multitude of additional effectors that together remodel the underlying cytoskeleton, culminating in internalization of the bound particle (5, 6).Phosphoinositide metabolism is thought to be critical for Fc␥R-induced phagocytosis (7,8). Highly localized and very dynamic phosphoinositide changes have been observed at sites of phagocytosis: phosphatidyli...

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The complement system in Aspergillus fumigatus infections and its crosstalk with pentraxins

et al. 2020

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Aspergillosis is a life-threatening infection mostly affecting immunocompromised individuals and primarily caused by the saprophytic fungus Aspergillus fumigatus. At the host-pathogen interface, both cellular and humoral components of the innate immune system are increasingly acknowledged as essential players in the recognition and disposal of this opportunistic mold. Fundamental hereof is the contribution of the complement system, which deploys all three activation pathways in the battle against A. fumigatus, and functionally cooperates with other soluble pattern recognition molecules, including pentraxins. In particular, preclinical and clinical observations point to the long pentraxin PTX3 as a nonredundant and complement-dependent effector with protective functions against A. fumigatus.Based on past and current literature, here we discuss how the complement participates in the immune response to this fungal pathogen, and illustrate its crosstalk with the pentraxins, with a focus on PTX3. Emphasis is placed on the molecular mechanisms underlying such processes, the genetic evidence from human epidemiology, and the translational potential of the currently available knowledge.Aspergillus fumigatus is an evolutionary ancient filamentous fungus (mold) that flourishes in soil and decomposing vegetation [1]. Traditionally regarded as asexual, the life cycle of this ubiquitous saprophyte actually comprises cryptic forms of sexual reproduction [2] and is hallmarked by several morphotypes with distinct metabolic, compositional, and structural traits [3]. The metabolically inactive and asexual airborne spores (known as dormant or resting conidia) are encased in a robust cell wall mostly made of complex polysaccharides [i.e., aand b-glucans, chitin, galactomannan (GM), and galactosaminogalactan (GAG)] in addition to lipids, proteins, and melanin pigments [i.e., dihydroxynaphthalene (DHN) melanin] [4]. Small in size (i.e., 2-3 µm across) and enveloped in a layer of hydrophobic rodlet-like proteins (i.e.

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Fcγ-receptors Induce Mac-1 (CD11b/CD18) Mobilization and Accumulation in the Phagocytic Cup for Optimal Phagocytosis

Cited by 110 publications

References 54 publications

Neutrophil integrin affinity regulation in adhesion, migration, and bacterial clearance

Neutrophil integrin affinity regulation in adhesion, migration, and bacterial clearance

Localized Diacylglycerol-dependent Stimulation of Ras and Rap1 during Phagocytosis

The complement system in Aspergillus fumigatus infections and its crosstalk with pentraxins

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