Expression of activated FcγRII discriminates between multiple granulocyte-priming phenotypes in peripheral blood of allergic asthmatic subjects

Kanters, Deon; Hove, Willem ten; Luijk, Bart; Aalst, Corneli van; Schweizer, René C.; Lammers, Jan‐Willem J.; Leufkens, Hubert G. M.; Raaijmakers, J. A. M.; Bracke, Madelon; Koenderman, Leo

doi:10.1016/j.jaci.2007.06.021

Cited by 41 publications

(56 citation statements)

References 46 publications

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“…The present results complement the steroid withdrawal study by demonstrating persistent ␤ 1 activation in dual responders with more eosinophilic inflammation in the airway. Blood eosinophils from dual responders, but not from single responders, have also been shown to have enhanced activation of Fc␥RII (CD32) as assessed with the phage mAb A17 6 h after challenge (42). Whether activation of ␤ 1 integrin and CD32 on circulating eosinophils are triggered by the same or different stimuli and signaling pathways is an interesting question that remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Up-Regulation and Activation of Eosinophil Integrins in Blood and Airway after Segmental Lung Antigen Challenge

Johansson¹,

Kelly

Busse

et al. 2008

The Journal of Immunology

117

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We hypothesized that there are clinically relevant differences in eosinophil integrin expression and activation in patients with asthma. To evaluate this, surface densities and activation states of integrins on eosinophils in blood and bronchoalveolar lavage (BAL) of 19 asthmatic subjects were studied before and 48 h after segmental Ag challenge. At 48 h, there was increased expression of αD and the N29 epitope of activated β1 integrins on blood eosinophils and of αM, β2, and the mAb24 epitope of activated β2 integrins on airway eosinophils. Changes correlated with the late-phase fall in forced expiratory volume in 1 s (FEV1) after whole-lung inhalation of the Ag that was subsequently used in segmental challenge and were greater in subjects defined as dual responders. Increased surface densities of αM and β2 and activation of β2 on airway eosinophils correlated with the concentration of IL-5 in BAL fluid. Activation of β1 and β2 on airway eosinophils correlated with eosinophil percentage in BAL. Thus, eosinophils respond to an allergic stimulus by activation of integrins in a sequence that likely promotes eosinophilic inflammation of the airway. Before challenge, β1 and β2 integrins of circulating eosinophils are in low-activation conformations and αDβ2 surface expression is low. After Ag challenge, circulating eosinophils adopt a phenotype with activated β1 integrins and up-regulated αDβ2, changes that are predicted to facilitate eosinophil arrest on VCAM-1 in bronchial vessels. Finally, eosinophils present in IL-5-rich airway fluid have a hyperadhesive phenotype associated with increased surface expression of αMβ2 and activation of β2 integrins.

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Section: Discussionmentioning

confidence: 99%

Up-Regulation and Activation of Eosinophil Integrins in Blood and Airway after Segmental Lung Antigen Challenge

Johansson¹,

Kelly

Busse

et al. 2008

The Journal of Immunology

117

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“…Among them are complement receptors (CR3, CR4), lymphocyte function-associated antigen-1 (LFA-1) and Fc fragment of IgG, low affinity II, receptor (FCGR2) [128]. FCGR2B can be of particular interest as it has been demonstrated to be upregulated in immune cells in acute and chronic mouse asthma models [27,[129][130][131].…”

Section: A C C E P T E D Article In Pressmentioning

confidence: 99%

Matrix metalloproteinase 12 silencing: A therapeutic approach to treat pathological lung tissue remodeling?

Garbacki¹,

Valentin²,

Piette³

et al. 2009

Pulmonary Pharmacology & Therapeutics

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“…[13][14][15][16] It remains unclear how Fc␥RI contributes to immune complex clearance in the presence of high IgG levels. For Fc␣RI 17,18 and Fc␥RIIa 19,20 it has been shown that cytokine stimulation can increase ligand binding of these receptors. This appears analogous to inside-out regulation described for integrins.…”

Section: Introductionmentioning

confidence: 99%

Cytokine-induced immune complex binding to the high-affinity IgG receptor, FcγRI, in the presence of monomeric IgG

Poel

Karssemeijer

Boross

et al. 2010

Blood

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IntroductionFc receptors are receptors for immunoglobulins that play a central role in immunity. On human leukocytes, a myriad of Fc␥ receptors are expressed; among these receptors, Fc␥RI is the only known high-affinity receptor for immunoglobulin G (IgG). 1 Fc␥RI is constitutively expressed on monocytes, macrophages, and myeloid dendritic cells. Interferon␥ (IFN␥) can enhance surface expression of Fc␥RI on these cells, and Fc␥RI expression can be induced on granulocytes by IFN␥ or granulocyte colony-stimulating factor (G-CSF) stimulation. In contrast, cytokines such as interleukin-4 (IL-4), IL-10, and transforming growth factor-␤ (TGF-␤) downregulate activating Fc receptors, including Fc␥RI, and enhance expression of the inhibitory receptor Fc␥RIIb. 2,3 In vitro, IFN␥ treatment leads to increased Fc␥ receptor-induced cytokine production. 4 In vivo, the role of Fc␥RI in immunity remains unclear, as due to its high affinity Fc␥RI is believed to be saturated with monomeric IgG. This has led to the concept that prebound monomeric IgG prevents participation of Fc␥RI in clearing immune complexes by extravasated effector cells. 5 Nevertheless, several in vivo studies documented a role for Fc␥RI, varying from a contribution during inflammation and autoimmune reactions, 6-8 or, during monoclonal antibody (mAb)-based immunotherapy in melanoma and B-cell lymphoma models, 9,10 to a malaria model in which transgenic expression of human Fc␥RI was central for effective mAb treatment. 11 Furthermore, Fc␥RI can induce potent proinflammatory signaling compared with Fc␥RIIa, 12 and can efficiently mediate both major histocompatibility complex class II (MHC-II) antigen presentation and cross-presentation. [13][14][15][16] It remains unclear how Fc␥RI contributes to immune complex clearance in the presence of high IgG levels. For Fc␣RI 17,18 and Fc␥RIIa 19,20 it has been shown that cytokine stimulation can increase ligand binding of these receptors. This appears analogous to inside-out regulation described for integrins. Many integrins are expressed in a low-affinity binding state, which can be transformed to a high-affinity form upon cellular activation. 21 We hypothesized that inside-out regulation could contribute to immune complex binding to Fc␥R occupied by IgG. Indeed, several studies support intracellular proteins interacting with Fc␥RI and possibly affecting ligand binding. 22,23 In this study, we investigated the effect of cytokine stimulation on Fc␥RI ligand binding. Stimulation of Fc␥RI-expressing Ba/F3 cells and primary monocytes resulted in increased binding of immune complexes, whereas binding of monomeric IgG was only moderately enhanced. Upon cellular activation, Fc␥RI could readily bind immune complexes despite pre-engaged monomeric IgG. Taken together, these data might explain how Fc␥RI supports leukocyte interaction with immune complexes. Methods Antibodies and reagentsAnti-Fc␥RI-A647 was from BioLegend (clone 10.1). Unlabeled 10.1 mAb and mouse IgG1/IgG2a isotype were from eBioscience and BD Pharmingen, respect...

show abstract

Expression of activated FcγRII discriminates between multiple granulocyte-priming phenotypes in peripheral blood of allergic asthmatic subjects

Cited by 41 publications

References 46 publications

Up-Regulation and Activation of Eosinophil Integrins in Blood and Airway after Segmental Lung Antigen Challenge

Up-Regulation and Activation of Eosinophil Integrins in Blood and Airway after Segmental Lung Antigen Challenge

Matrix metalloproteinase 12 silencing: A therapeutic approach to treat pathological lung tissue remodeling?

Cytokine-induced immune complex binding to the high-affinity IgG receptor, FcγRI, in the presence of monomeric IgG

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