Identification of Antigen-Capturing Cells as Basophils

Mack, Matthias; Schneider, Martin; Moll, Cordula; Cihak, Josef; Brühl, Hilke; Ellwart, Joachim W.; Hogarth, P. Mark; Stangassinger, M.; Schlöndorff, Detlef

doi:10.4049/jimmunol.174.2.735

Cited by 67 publications

(49 citation statements)

References 32 publications

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“…[19][20][21] Furthermore, CCR2 is also expressed on endothelial cells during inflammation, consistent with a potential role in wound repair. 22 Information regarding the expression of CCR2 on non-hematopoietic cells in the CNS is currently limited and inconsistent.…”

Section: Expression Of Ccr2mentioning

confidence: 77%

Role of CCR2 in Inflammatory Conditions of the Central Nervous System

Chu

Arumugam

Gelderblom

et al. 2014

J Cereb Blood Flow Metab

137

106

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CC chemokine receptor 2 (CCR2) plays important roles in extravasation and transmigration of monocytes under inflammatory conditions. CCR2 and its ligands have been extensively studied in a range of inflammatory diseases in the central nervous system (CNS), including multiple sclerosis, Alzheimer's disease and ischemic stroke. This brief review summarizes our current understanding of the physiologic and pathologic roles of CCR2, focusing on its involvement in CNS inflammatory diseases. There appears to be a rationale for exploring therapies involving CCR2 inhibition in multiple sclerosis and ischemic stroke, but there is also evidence for immunomodulatory and protective effects of CCR2 activity during CNS inflammation. The critical balance between protective and detrimental roles of CCR2-dependent recruitment of leukocytes must therefore be carefully examined to guide safe and effective development of any therapies involving CCR2 modulation.

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Section: Expression Of Ccr2mentioning

confidence: 77%

Role of CCR2 in Inflammatory Conditions of the Central Nervous System

Chu

Arumugam

Gelderblom

et al. 2014

J Cereb Blood Flow Metab

137

106

View full text Add to dashboard Cite

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“…It has been thought that basophils are predominant Ag-capturing cells (41), and that Ag and Ag-specific IgE complexes activate basophils to produce IL-4 and IL-6, leading to enhanced humoral memory immune responses (7). However, a recent report showed that basophil-deficient mice still have efficient humoral immune responses (14).…”

Section: Discussionmentioning

confidence: 92%

“…During secondary Ag exposure, Ag-specific, IgE-bearing basophils capture Ag, become activated, and secrete cytokines, which subsequently facilitates memory B cell responses (7,41). Although WT and Sema4B 2/2 basophils produced comparable levels of IL-4 and IL-6 on FcεRI cross-linking (Supplemental Fig.…”

Section: /2 Mice Have Enhanced Ige Memory Responsesmentioning

confidence: 99%

Identification of Semaphorin 4B as a Negative Regulator of Basophil-Mediated Immune Responses

Nakagawa

Takamatsu

Okuno

et al. 2011

The Journal of Immunology

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Basophils are strong mediators of Th2 responses during helminthic infections. Recently, basophils were shown to function as APCs and promote both Th2 skewing and humoral memory responses. However, the mechanisms that regulate basophils are still unclear. In this article, we show that a class IV semaphorin, Sema4B, negatively regulates basophil functions through T cell–basophil contacts. In a screen to identify semaphorins that function in the immune system, we determined that Sema4B is expressed in T and B cells. Interestingly, Sema4B−/− mice had considerably increased serum IgE levels despite normal lymphocyte and dendritic cell functions. Recombinant Sema4B significantly inhibited IL-4 and IL-6 production from basophils in response to various stimuli, including IL-3, papain, and FcεRI cross-linking. In addition, T cell-derived Sema4B, which accumulated at contact sites between basophils and CD4+ T cells, suppressed basophil-mediated Th2 skewing, suggesting that Sema4B regulates basophil responses through cognate cell–cell contacts. Furthermore, Sema4B−/− mice had enhanced basophil-mediated memory IgE production, which was abolished by treating with an anti-FcεRIα Ab. Collectively, these results indicate that Sema4B negatively regulates basophil-mediated Th2 and humoral memory responses.

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“…Bovine type II collagen (Sigma C1188; St. Louis, MO) was dissolved overnight in 0.1M acetic acid at a concentration of 2 mg/ml and, for the first injection, was emulsified in an equal volume of Freund's complete adjuvant. Male DBA/1 mice were immunized with an intra-/subcutaneous injection of 100 l emulsion at the base of the tail on day 0, and an intraperitoneal (IP) injection of 100 g type II collagen without adjuvant at day 21 Histology. Hind paws were fixed in 3.7% formalin for 24 hours, washed in PBS, and decalcified with RDO rapid decalcifier (Medite, Burgdorf, Germany).…”

Section: Methodsmentioning

confidence: 99%

Targeting of Gr‐1+,CCR2+ monocytes in collagen‐induced arthritis

Brühl¹,

Cihak²,

Plachý

et al. 2007

Arthritis & Rheumatism

Self Cite

109

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Objective. The chemokine receptor CCR2 is highly expressed on monocytes and considered a promising target for treatment of rheumatoid arthritis. However, blockade of CCR2 with a monoclonal antibody (mAb) during progression of collagen-induced arthritis results in a massive aggravation of the disease. In this study we investigated why CCR2 antibodies have proinflammatory effects, how these effects can be avoided, and whether CCR2؉ monocytes are useful targets in the treatment of arthritis.Methods. Arthritis was induced in DBA/1 mice by immunization with type II collagen. Mice were treated with mAb against CCR2 (MC-21), IgE, or isotype control antibodies at various time points. Activation of basophils and depletion of monocyte subsets were determined by fluorescence-activated cell sorter analysis and enzyme-linked immunosorbent assay.Results. Crosslinkage of CCR2 activated basophils to release interleukin-6 (IL-6) and IL-4. In vivo, IL-6 release occurred only after exposure to high doses of MC-21, whereas application of low doses of the mAb circumvented the release of IL-6. Regardless of the dose level used, the antibody MC-21 efficiently depleted Gr-1؉,CCR2؉ monocytes from the synovial tissue, peripheral blood, and spleen of DBA/1 mice. Activation of basophils with high doses of MC-21 or with antibodies against IgE resulted in a marked aggravation of collagen-induced arthritis and an increased release of IL-6. In contrast, low-dose treatment with MC-21 in this therapeutic setting had no effect on IL-6 and led to marked improvement of arthritis.Conclusion. These results show that depletion of CCR2؉ monocytes may prove to be a therapeutic option in inflammatory arthritis, as long as the dosedependent proinflammatory effects of CCR2 mAb are taken into account.CCR2, a chemokine (CC motif) receptor, is considered a promising target for disorders such as multiple sclerosis, type II diabetes, and rheumatoid arthritis, and Phase I and II clinical trials are currently in progress (1). Data on CCR2 expression in humans and results from studies of CCR2-deficient mice (2-4) support the blockade of CCR2 as an effective strategy in the treatment of multiple sclerosis and diabetes. In patients with rheumatoid arthritis, we and other investigators have found an increased frequency of CCR2ϩ cells in the synovial fluid and synovial tissue (5-7). In addition, increased levels of the CCR2 ligand monocyte chemoattractant protein 1 (MCP-1; CCL2) were found in patients with rheumatoid arthritis (8). Monocytes are thought to play a major role in joint destruction, and their recruitment to sites of inflammation is crucially dependent on CCR2, as shown in several murine disease models (9-12).However, thus far, data from murine models of collagen-induced arthritis do not support CCR2 as a target for treatment of rheumatoid arthritis. We have previously shown that treatment with a blocking monoDrs. Brühl, Luckow,

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Identification of Antigen-Capturing Cells as Basophils

Cited by 67 publications

References 32 publications

Role of CCR2 in Inflammatory Conditions of the Central Nervous System

Role of CCR2 in Inflammatory Conditions of the Central Nervous System

Identification of Semaphorin 4B as a Negative Regulator of Basophil-Mediated Immune Responses

Targeting of Gr‐1+,CCR2+ monocytes in collagen‐induced arthritis

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