Chemokine and cytokine cooperativity: Eosinophil migration in the asthmatic response

Simson, Ljubov; Foster, Paul S.

doi:10.1046/j.1440-1711.2000.00922.x

Cited by 44 publications

(38 citation statements)

References 54 publications

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“…The importance of eotaxin together with IL-5 in promoting the initial movement of eosinophils into airway tissue in asthma is not in dispute (30); however, our findings suggest that eotaxin may be ineffective at a later stage in the process, i.e., adhesion of eosinophils to airway epithelium. We showed previously that eotaxin increased eosinophil adhesion to human lung microvascular endothelial cells via activation of ␤ 2 and ␣ 4 ␤ 1 integrins and adhesion to ICAM-1 and VCAM-1, respectively (41).…”

Section: Discussionmentioning

confidence: 55%

“…Soluble mediators such as the cytokines IL-5 and IL-3 prime eosinophil function, one example being degranulation of C5a-activated eosinophils (29). The synergistic effect between IL-5 and eotaxin to promote eosinophil migration in asthma is also well recognized (30). In addition to soluble mediators, adhesion molecules and in particular leukocyte integrins can also provide priming signals to eosinophils (31,32).…”

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confidence: 99%

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TNF-α Potentiates C5a-Stimulated Eosinophil Adhesion to Human Bronchial Epithelial Cells: A Role for α5β1 Integrin

Burke‐Gaffney

Blease²,

Hartnell³

et al. 2002

The Journal of Immunology

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Cooperative action of inflammatory mediators and adhesion molecules orchestrates eosinophil recruitment during allergic inflammation in the airways. This study investigated the mechanisms involved in increasing eosinophil adhesion to human bronchial epithelial cells (HBEC) following priming and activation of eosinophils with TNF-α and complement protein C5a, respectively. Under primed conditions, eosinophil adhesion increased 3-fold from basal (16%), and the effect was significantly greater (p < 0.05) than the increase following stimulation with C5a alone (2-fold). Eosinophil contact with HBEC was essential for priming. In contrast to C5a, adhesion of eotaxin-stimulated eosinophils to HBEC was not primed with TNF-α nor IL-5, a known eosinophil-priming agent. Priming caused activation of αMβ2 integrin; mAb against either the common β2 integrin subunit or its ICAM-1 ligand reduced the primed component of adhesion. Using mAbs against β1 or α5, but not α4 integrin subunit, together with anti-β2 integrin mAb, reduced stimulated adhesion to basal levels. Cross-linking α5β1 integrin increased αMβ2 integrin-dependent adhesion of eosinophils. There are no known adhesion molecule ligands of α5β1 integrin expressed on HBEC; however, fibronectin, the major matrix protein ligand for α5β1 integrin, was detected in association with HBEC monolayers. A mAb against fibronectin, in combination with anti-β2 integrin mAb, reduced adhesion to basal levels. In conclusion, α5β1 integrin may provide a contact-dependent costimulus for eosinophil priming that, together with TNF-α, potentiated C5a activation of αMβ2 integrin and increased eosinophil adhesion to ICAM-1. Fibronectin, associated with HBEC, may act as a ligand for α5β1 integrin. Dual regulation of eosinophil priming may prevent inappropriate activation of eosinophils in the circulation.

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Section: Discussionmentioning

confidence: 55%

mentioning

confidence: 99%

TNF-α Potentiates C5a-Stimulated Eosinophil Adhesion to Human Bronchial Epithelial Cells: A Role for α5β1 Integrin

Burke‐Gaffney

Blease²,

Hartnell³

et al. 2002

The Journal of Immunology

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“…In fact, synergy between cytokines and chemokines has been previously observed in proliferation, differentiation, and survival assays as well as in migration experiments. 27,[52][53][54][55] Our findings showing increased migration when cells were stimulated with 2-AG and IL-3 as well as 2-AG and G-CSF strengthen the idea to further investigate the role that 2-AG may have in combination with cytokines in proliferation, differentiation, or survival of leukemic progenitor cells.…”

Section: Discussionmentioning

confidence: 64%

Hematopoietic cells expressing the peripheral cannabinoid receptor migrate in response to the endocannabinoid 2-arachidonoylglycerol

Jordà

Verbakel

Valk

et al. 2002

Blood

149

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Cb2 is a novel protooncogene encoding the peripheral cannabinoid receptor. Previous studies demonstrated that 2 distinct noncoding first exons exist: exon-1A and exon-1B, which both splice to proteincoding exon-2. We demonstrate that in retrovirally induced murine myeloid leukemia cells with proviral insertion in Cb2, exon-1B/exon-2 Cb2 messenger RNA levels have been increased, resulting in high receptor numbers. In myeloid leukemia cells without virus insertion in this locus, low levels of only exon-1A/exon-2 Cb2 transcripts were present and receptors could not be detected. To elucidate the function of Cb2 in myeloid leukemia cells, a set of in vitro experiments was carried out using 32D/G-CSF-R (granulocyte colony-stimulating factor receptor) cells transfected with exon-1B/exon-2 Cb2 complementary DNA and a myeloid cell line carrying a virus insertion in Cb2 (ie, NFS 78). We demonstrate that a major function of the Cb2 receptor is stimulation of migration as determined in a transwell assay. The cannabinoid receptors belong to the superfamily of 7-transmembrane G protein-coupled receptors (GPCRs). Several GPCRs have been shown to be involved in cell growth and oncogenesis as the result of aberrant expression. [5][6][7] Examples of GPCRs with transforming ability are the ␣1B-adrenergic, 8 thrombin, 9 and serotonin 1c receptors 10 and the receptor encoded by MAS oncogene. 11,12 Our previous observation that Cb2 is a common virus integration site suggests that aberrant expression of this 7-transmembrane receptor may be a critical event in transformation in certain cases of leukemia. 3 The protein-coding region of Cb2 is located on a single exon (exon-2) of approximately 4 kilobases. Recently we identified 2 distinct 5Ј noncoding exons (ie, exon-1A and exon-1B) previously designated exon-1 and exon-1Ј, respectively. 3 In the study presented here we first carried out experiments to investigate Cb2 messenger RNA (mRNA) transcripts and protein expression in leukemic cells with or without retroviral insertion in the Cb2 locus. Secondly, we performed studies to determine the function of the peripheral cannabinoid receptor when overexpressed in myeloid cells.GPCRs have been related to many functions, including cell proliferation, maturation, survival, apoptosis, or migration. 6,13,14 In the present study, we investigated the function of the peripheral cannabinoid receptor when overexpressed on myeloid cells (ie, 32D/G-CSF-R [granulocyte colony-stimulating factor receptor]) in which we overexpressed exon-1B/exon-2 Cb2 splice variant and a myeloid leukemia cell line containing a virus insertion in the Cb2 locus, NFS 78. We also wished to determine which of the large panel of Cb2 ligands that have been identified previously is the true agonist of the receptor. We investigated the effects of natural (␦ 8 24 ) cannabinoids. We show that 2-AG is the most potent agonist for the Cb2 receptor and that a major function of 2-AG is stimulation of migration. We further studied whether 2-AG acts as a chemotactic or chemokinetic age...

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“…osinophils are thought to play an important role in the pathobiology of asthma due to their capability to release molecules inducing tissue damage and amplifying the allergic inflammatory reaction (1)(2)(3)(4). Mechanisms responsible for eosinophil transmigration into the lung have been well characterized in terms of adhesion molecules implicated in eosinophil-endothelium interaction, chemotactic stimuli implicated in selective eosinophil recruitment, and factors regulating eosinophil differentiation and priming (3)(4)(5)(6).…”

mentioning

confidence: 99%

“…Mechanisms responsible for eosinophil transmigration into the lung have been well characterized in terms of adhesion molecules implicated in eosinophil-endothelium interaction, chemotactic stimuli implicated in selective eosinophil recruitment, and factors regulating eosinophil differentiation and priming (3)(4)(5)(6). However, the intracellular signal transduction pathways triggered by adhesion receptors, receptors for lipid-derived chemoattractants and chemokines, and receptors for eosinophil-active cytokines are less well understood.…”

mentioning

confidence: 99%

Fgr Deficiency Results in Defective Eosinophil Recruitment to the Lung During Allergic Airway Inflammation

Vicentini

Mazzi²,

Caveggion³

et al. 2002

The Journal of Immunology

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Using a mouse model of allergic lung inflammation, we found that mice deficient of Fgr, a Src family tyrosine kinase highly expressed in myelomonocytic cells, fail to develop lung eosinophilia in response to repeated challenge with aerosolized OVA. Both tissue and airway eosinophilia were markedly reduced in fgr−/− mice, whereas mice with the sole deficiency of Hck, another Src family member, responded normally. Release of allergic mediators, such as histamine, IL-4, RANTES/CCL5, and eotaxin/CCL11, in the airways of OVA-treated animals was equal in wild-type and fgr−/− mice. However, lung eosinophilia in Fgr-deficient mice correlated with a defective accumulation of GM-CSF and IL-5 in the airways, whereas secretion of these cytokines by spleen cells in response to OVA was normal. Examination of mRNA expression in whole lung tissue allowed us to detect comparable expression of transcripts for eotaxin/CCL11, macrophage-inflammatory protein-1α/CCL3, macrophage-inflammatory protein-1β/CCL4, monocyte chemoattractant protein-1/CCL2, TCA-3/CCL1, IL-4, IL-10, IL-2, IL-3, IL-9, IL-15, and IFN-γ in OVA-sensitized wild-type and fgr−/− mice. In contrast, the increase in IL-5 and IL-13 mRNA expression was lower in fgr−/− compared with wild-type mice. These findings suggest that deficiency of Fgr results in a marked reduction of lung eosinophilia and the establishment of a positive feedback loop based on autocrine secretion of eosinophil-active cytokines. These results identify Fgr as a novel pharmacological target to control allergic inflammation.

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Chemokine and cytokine cooperativity: Eosinophil migration in the asthmatic response

Cited by 44 publications

References 54 publications

TNF-α Potentiates C5a-Stimulated Eosinophil Adhesion to Human Bronchial Epithelial Cells: A Role for α5β1 Integrin

TNF-α Potentiates C5a-Stimulated Eosinophil Adhesion to Human Bronchial Epithelial Cells: A Role for α5β1 Integrin

Hematopoietic cells expressing the peripheral cannabinoid receptor migrate in response to the endocannabinoid 2-arachidonoylglycerol

Fgr Deficiency Results in Defective Eosinophil Recruitment to the Lung During Allergic Airway Inflammation

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