RANTES Induces Nasal Mucosal Inflammation Rich in Eosinophils, Basophils, and Lymphocytes<i>In Vivo</i>

Kuna, Piotr; Alam, Rafeul; Ruta, U; Górski, Paweł

doi:10.1164/ajrccm.157.3.9610052

Cited by 67 publications

(49 citation statements)

References 40 publications

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“…In addition, intradermal injection of human RANTES into allergic human subjects was shown to cause a rich eosinophil recruitment into the skin in vivo (78). In another human study, intranasal administration of RANTES into allergic rhinitis patients resulted in an inflammatory infiltrate into the nasal mucosa that was rich in eosinophils (79). Furthermore, we and others have demonstrated that this ␤-chemokine binds to CCR3 on human eosinophils and stimulates signal transduction through CCR3 with high potency (7,8,27).…”

Section: Discussionmentioning

confidence: 91%

Functional Expression and Characterization of Macaque C-C Chemokine Receptor 3 (CCR3) and Generation of Potent Antagonistic Anti-macaque CCR3 Monoclonal Antibodies

Zhang

Soares

Guan

et al. 2002

Journal of Biological Chemistry

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Eosinophils are major effector cells implicated in a number of chronic inflammatory diseases in humans, particularly bronchial asthma and allergic rhinitis. The ␤-chemokine receptor C-C chemokine receptor 3 (CCR3) provides a mechanism for the selective recruitment of eosinophils into tissue and thus has recently become an attractive biological target for therapeutic intervention. In order to develop in vivo models of inflammatory diseases, it is essential to identify and characterize the homologues of human eotaxin (C-C chemokine ligand 11) and CCR3 from other species, such as non-human primates. Accordingly, we cloned the macaque eotaxin and CCR3 genes and revealed that they were 91 and 92% identical at the amino acid level to their human homologues, respectively. Macaque CCR3 expressed in the murine pre-B L1-2 cell line bound macaque eotaxin with high affinity (K d ‫؍‬ 0.1 nM) and exhibited a robust eotaxin-induced Ca 2؉ flux and chemotaxis. Characterization of ␤-chemokines on native macaque CCR3 on eosinophils was performed by means of eotaxin-induced shape change in whole blood using a novel signaling assay known as gated autofluorescence forward scatter. Additionally, mAbs were raised against macaque CCR3 using two different immunogens: a 30-amino acid synthetic peptide derived from the predicted NH 2 terminus of macaque CCR3 and intact macaque CCR3-transfected cells. These anti-macaque CCR3 monoclonal antibodies exhibited potent antagonist activity in receptor binding and functional assays. The characterization of the macaque eotaxin/CCR3 axis and development of antagonistic anti-macaque CCR3 monoclonal antibodies will facilitate the development of CCR3 small molecule antagonists with the hope of ameliorating chronic inflammatory diseases in humans.

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Section: Discussionmentioning

confidence: 91%

Functional Expression and Characterization of Macaque C-C Chemokine Receptor 3 (CCR3) and Generation of Potent Antagonistic Anti-macaque CCR3 Monoclonal Antibodies

Zhang

Soares

Guan

et al. 2002

Journal of Biological Chemistry

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“…Local production or delivery of RANTES has been shown to cause chemotaxis of immune cells in vivo (6,31). The mucosa contain large numbers of ␥␦ TCR ϩ intraepithelial lymphocytes (32), which secrete RANTES and other chemokines in response to stimulation (33).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, human nasal-and adenoid-derived epithelial cells have been shown to secrete chemokines such as IL-8, monocyte chemoattractant protein-1 and RANTES in response to infection with respiratory syncytial virus (3,4). RANTES is a CC chemokine that binds CCR1, CCR3, CCR4, and CCR5 and is produced by epithelial cells (3)(4)(5)(6)(7)(8), lymphocytes (9,10), and platelets (11), and acts as a potent chemoattractant for monocytes (12,13), NK cells (14), memory T cells (12,13,15), eosinophils (11), dendritic cells (16), and basophils (17). In addition, RANTES and other chemokines can selectively activate their corresponding lymphoid cell targets (14, 18 -21).…”

mentioning

confidence: 99%

“…RANTES has been shown to induce lymphocyte migration into the nasal mucosa of allergic patients (6) and its expression can be induced by infecting human bronchial tissue-or nasal polyp-derived epithelial cells with influenza virus (7). Freshly isolated human colon epithelial cells and HT-29 and Caco-2 epithelial tumor cell lines were shown to secrete RANTES and other chemokines in response to Salmonella typhimurium infection or cytokine stimulation (5).…”

mentioning

confidence: 99%

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RANTES Potentiates Antigen-Specific Mucosal Immune Responses

Lillard

Boyaka

Taub

et al. 2001

The Journal of Immunology

106

105

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RANTES is produced by lymphoid and epithelial cells of the mucosa in response to various external stimuli and is chemotactic for lymphocytes. The role of RANTES in adaptive mucosal immunity has not been studied. To better elucidate the role of this chemokine, we have characterized the effects of RANTES on mucosal and systemic immune responses to nasally coadministered OVA. RANTES enhanced Ag-specific serum Ab responses, inducing predominately anti-OVA IgG2a and IgG3 followed by IgG1 and IgG2b subclass Ab responses. RANTES also increased Ag-specific Ab titers in mucosal secretions and these Ab responses were associated with increased numbers of Ab-forming cells, derived from mucosal and systemic compartments. Splenic and mucosally derived CD4+ T cells of RANTES-treated mice displayed higher Ag-specific proliferative responses and IFN-γ, IL-2, IL-5, and IL-6 production than control groups receiving OVA alone. In vitro, RANTES up-regulated the expression of CD28, CD40 ligand, and IL-12R by Ag-activated primary T cells from DO11.10 (OVA-specific TCR-transgenic) mice and by resting T cells in a dose-dependent fashion. These studies suggest that RANTES can enhance mucosal and systemic humoral Ab responses through help provided by Th1- and select Th2-type cytokines as well as through the induction of costimulatory molecule and cytokine receptor expression on T lymphocytes. These effects could serve as a link between the initial innate signals of the host and the adaptive immune system.

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“…Studies in humans and animals indicate that MCP-3, RANTES, and eotaxin are all present at significantly increased levels in either airways or skin of allergic subjects after allergen challenge (29 -31). In vivo challenge models using RANTES or eotaxin have resulted in an eosinophil-rich inflammatory infiltrate in both animals (32) and humans (33,34). Furthermore, the expression of these chemokines is associated with the accumulation of eosinophils at the sites of allergic inflammation (12,(35)(36)(37).…”

mentioning

confidence: 99%

Migration of Eosinophils Across Endothelial Cell Monolayers: Interactions Among IL-5, Endothelial-Activating Cytokines, and C-C Chemokines

Shahabuddin

Ponath

Schleimer

2000

The Journal of Immunology

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Eosinophils are the predominant cell type recruited in inflammatory reactions in response to allergen challenge. The mechanisms of selective eosinophil recruitment in allergic reactions are not fully elucidated. In this study, the ability of several C-C chemokines to induce transendothelial migration (TEM) of eosinophils in vitro was assessed. Eotaxin, eotaxin-2, monocyte chemotactic protein (MCP)-4, and RANTES induced eosinophil TEM across unstimulated human umbilical vein endothelial cells (HUVEC) in a concentration-dependent manner with the following rank order of potency: eotaxin ≈ eotaxin-2 > MCP-4 ≈ RANTES. The maximal response induced by eotaxin or eotaxin-2 exceeded that of RANTES or MCP-4. Preincubation of eosinophils with anti-CCR3 Ab (7B11) completely blocked eosinophil TEM induced by eotaxin, MCP-4, and RANTES. Activation of endothelial cells with IL-1β or TNF-α induced concentration-dependent migration of eosinophils, which was enhanced synergistically in the presence of eotaxin and RANTES. Anti-CCR3 also inhibited eotaxin-induced eosinophil TEM across TNF-α-stimulated HUVEC. The ability of eosinophil-active cytokines to potentiate eosinophil TEM was assessed by investigating eotaxin or RANTES-induced eosinophil TEM across resting and IL-1β-stimulated HUVEC in the presence or absence of IL-5. The results showed synergy between IL-5 and the chemokines but not between IL-5 and the endothelial activator IL-1β. Our data suggest that eotaxin, eotaxin-2, MCP-4, and RANTES induce eosinophil TEM via CCR3 with varied potency and efficacy. Activation of HUVEC by IL-1β or TNF-α or priming of eosinophils by IL-5 both promote CCR3-dependent migration of eosinophils from the vasculature in conjunction with CCR3-active chemokines.

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RANTES Induces Nasal Mucosal Inflammation Rich in Eosinophils, Basophils, and LymphocytesIn Vivo

Cited by 67 publications

References 40 publications

Functional Expression and Characterization of Macaque C-C Chemokine Receptor 3 (CCR3) and Generation of Potent Antagonistic Anti-macaque CCR3 Monoclonal Antibodies

Functional Expression and Characterization of Macaque C-C Chemokine Receptor 3 (CCR3) and Generation of Potent Antagonistic Anti-macaque CCR3 Monoclonal Antibodies

RANTES Potentiates Antigen-Specific Mucosal Immune Responses

Migration of Eosinophils Across Endothelial Cell Monolayers: Interactions Among IL-5, Endothelial-Activating Cytokines, and C-C Chemokines

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