Differential roles of Fc gamma RII and Fc gamma RIII in immune complex stimulation of human neutrophils.

Brunkhorst, Beatrice; Strohmeier, G; Lazzari, K G; Weil, Gary J.; Melnick, David; Fleit, Howard B.; Simons, Elizabeth R.

doi:10.1016/s0021-9258(19)36736-5

Cited by 42 publications

(4 citation statements)

References 54 publications

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“…PMN eventually move into a postapoptotic phase, during which there is loss of cell membrane integrity. (33,34). In binding of ANCA to the surface of an apoptotic PMN, Fc-dependent bridging could occur via Fc␥-RIIa on a nonapoptotic PMN as in current models (9,28,31,32) or, alternatively, via Fc␥RIIa on a second or the same apoptotic PMN, since apoptotic PMN have been shown to express normal levels of Fc␥RIIa (35).…”

Section: Discussionmentioning

confidence: 99%

Antineutrophil Cytoplasmic Autoantibodies Interact with Primary Granule Constituents on the Surface of Apoptotic Neutrophils in the Absence of Neutrophil Priming

Gilligan

Bredy

Brady

et al. 1996

The Journal of Experimental Medicine

140

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The pathogenic role of antineutrophil cytoplasmic autoantibodies (ANCA) remains controversial because of the difficulty in explaining how extracellular ANCA can interact with intracellular primary granule constituents. It has been postulated that cytokine priming of neutrophils (PMN), as may occur during a prodromal infection, is an important trigger for mobilization of granules to the cell surface, where they may interact with ANCA. We show by electron microscopy that apoptosis of unprimed PMN is also associated with the translocation of cytoplasmic granules to the cell surface and alignment just beneath an intact cell membrane. Immunofluorescent microscopy and FACS® analysis demonstrate reactivity of ANCA-positive sera and antimyeloperoxidase antibodies with apoptotic PMN, but not with viable PMN. Moreover, we show that apoptotic PMN may be divided into two subsets, based on the presence or absence of granular translocation, and that surface immunogold labeling of myeloperoxidase occurs only in the subset of PMN showing translocation. These results provide a novel mechanism that is independent of priming, by which ANCA may gain access to PMN granule components during ANCA-associated vasculitis.

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Section: Discussionmentioning

confidence: 99%

Antineutrophil Cytoplasmic Autoantibodies Interact with Primary Granule Constituents on the Surface of Apoptotic Neutrophils in the Absence of Neutrophil Priming

Gilligan

Bredy

Brady

et al. 1996

The Journal of Experimental Medicine

140

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“…Recent studies have demonstrated that NHE-1 is a calmodulin-binding protein and the concentration of intracellular Ca2÷ ([Ca2+]i) can regulate the activity of NHE-1 in flbroblasts (Bertrand et al, 1994). It is also noteworthy that many of the conditions leading to NHE activation including phagocytosis (Rosales and Brown, 1991), Fc~/receptor cross-linking (Huizinga et at., 1990;Brunkhorst et al, 1992;Della Bianca et al, 1993;G r a h a m et al, 1993;Naziruddin et al, 1992;Rosales and Brown, 1992;and Fig. 6 e), and stimulation with fMLP also result in an increase in [Ca2+]i.…”

Section: Signaling Pathways Involved In Nhe Activationmentioning

confidence: 92%

Na+/H+ exchange activity during phagocytosis in human neutrophils: role of Fcgamma receptors and tyrosine kinases.

Fukushima

Waddell

Grinstein

et al. 1996

The Journal of Cell Biology

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Abstract. In neutrophils, binding and phagocytosis facilitate subsequent intracellular killing of microorganisms. Activity of Na+/H ÷ exchangers (NHEs) participates in these events, especially in regulation of intracellular pH (pHi) by compensating for the H ÷ load generated by the respiratory burst. Despite the importance of these functions, comparatively little is known regarding the nature and regulation of NHE(s) in neutrophils. The purpose of this study was to identify which NHE(s) are expressed in neutrophils and to elucidate the mechanisms regulating their activity during phagocytosis. Exposure of cells to the phagocytic stimulus opsonized zymosan (OpZ) induced a transient cytosolic acidification followed by a prolonged alkalinization. The latter was inhibited in Na+-free medium and by amiloride analogues and therefore was due to activation of Na+/H + exchange. Reverse transcriptase PCR and cDNA sequencing demonstrated that mRNA for the NHE-1 but not for NHE-2, 3, or 4 isoforms of the exchanger was expressed. Immunoblotting of purified plasma membranes with isoform-specific antibodies confirmed the presence of NHE-1 protein in neutrophils. Since phagocytosis involves Fc~/(Fc~R) and complement receptors such as CR3 (a 132 integrin) which are linked to pathways involving alterations in intracellular [Ca2+]i and tyrosine phosphorylation, we studied these pathways in relation to activation of NHE-1. Cross-linking of surface bound antibodies (mAb) directed against Fc~/Rs (Fc-,/RII > Fc-yRIII) but not 132 integrins induced an amiloride-sensitive cytosolic alkalinization. However, anti-132 integrin mAb diminished OpZ-induced alkalinization suggesting that NHE-1 activation involved cooperation between integrins and Fc~Rs. The tyrosine kinase inhibitors genistein and herbimycin blocked cytosolic alkalinization after OpZ or FcvR cross-linking suggesting that tyrosine phosphorylation was involved in NHE-1 activation. An increase in [Ca2+]i was not required for NHE-1 activation because neither removal of extracellular Ca 2÷ nor buffering of changes in [Ca2+]i inhibited alkalinization after OpZ or Fc~R cross-linking. In summary, Fc~/Rs and 132 integrins cooperate in activation of NHE-1 in neutrophils during phagocytosis by a signaling pathway involving tyrosine phosphorylation. NEUTROPmLS react to invading microorganisms and mediators present within an inflammatory milieu with a variety of rapid and coordinated responses which include movement of cells out of the vascular space along a gradient of chemotactic molecules followed by phagocytosis and killing of the microorganisms. This bactericidal function is effected by complex processes involving secretion of proteolytic enzymes and reactive oxygen intermediates (produced by the NADPH oxidase) into the phagolysosome (for review see Sha'afi and Molski, 1988). During these processes, dynamic alterations occur in leu-

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“…IC-specific degranulation requires incorporation of complement followed by binding to neutrophil Fcg and complement receptors. 24 To understand the mechanism of anti-PF4/heparin IC-induced neutrophil activation in our assay, we examined the role of FcgRIIa, which mediates platelet 25 and neutrophil activation, 26 and complement, which is activated by ICs. 24 As shown in Figure 4, when whole blood is pre-incubated with IV.3 (a monoclonal antibody to human CD32 which blocks cellular FcgRIIa), there is a 63% decline in KKO-PF4/heparin-induced neutrophil degranulation.…”

Section: Kko-pf4/heparin-induced Neutrophil Activation Is Mediated By Cellular Fcgriia and Complementmentioning

confidence: 99%

Heterogeneity in neutrophil responses to immune complexes

Duarte¹,

Kuchibhatla

Khandelwal³

et al. 2019

Blood Advances

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Differential roles of Fc gamma RII and Fc gamma RIII in immune complex stimulation of human neutrophils.

Cited by 42 publications

References 54 publications

Antineutrophil Cytoplasmic Autoantibodies Interact with Primary Granule Constituents on the Surface of Apoptotic Neutrophils in the Absence of Neutrophil Priming

Antineutrophil Cytoplasmic Autoantibodies Interact with Primary Granule Constituents on the Surface of Apoptotic Neutrophils in the Absence of Neutrophil Priming

Na+/H+ exchange activity during phagocytosis in human neutrophils: role of Fcgamma receptors and tyrosine kinases.

Heterogeneity in neutrophil responses to immune complexes

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