Eosinophils: Biological Properties and Role in Health and Disease

Background: Although we first found galectin-9 (Gal-9) as an eosinophil chemoattractant, its role in eosinophilic inflammation is still obscure. The purpose of the present study is to clarify the role of Gal-9 in human eosinophilic pulmonary inflammation in comparison with eotaxin (CCL11). Methods: We measured the levels of Gal-9 and eotaxin in the bronchoalveolar lavage fluid (BALF) of patients with acute and chronic eosinophilic pneumonia (AEP and CEP). Furthermore, the biological activities (chemotaxis and apoptosis) of Gal-9 were compared with those of eotaxin using interleukin-5-primed or -unprimed eosinophils. Results: The levels of Gal-9 and eotaxin in the BALF from patients with AEP and those with CEP were higher than those found in the controls. Although there was little difference in Gal-9 level between patients with AEP and patients with CEP, the eotaxin level was significantly lower in patients with CEP. In patients with AEP, the eosinophil number correlated well with both the Gal-9 and eotaxin levels. However, in patients with CEP, the eosinophil number only correlated well with the Gal-9 level. Moreover, the Gal-9 level correlated with the eotaxin level in patients with AEP, but there was no significant correlation between those levels in patients with CEP. Anti-Gal-9 antibody treatment strongly reduces eosinophil chemotactic activity in the BALF of patients with AEP and in that of patients with CEP, whereas the anti-CCR3 (receptor for eotaxin) antibody strongly reduces this activity in the BALF of patients with AEP but not in that of patients with CEP. Furthermore, Gal-9 exhibited both chemotactic and proapoptotic activities for activated eosinophils, though eotaxin only exhibited chemotactic activity. Conclusions: The present results provide two possibilities: that Gal-9 is involved in pulmonary eosinophilia in patients with AEP and CEP, and that Gal-9 exhibits regulatory functions for activated eosinophils at the site of inflammation.

Section: Discussionmentioning

confidence: 99%

Involvement of Galectin-9 in Lung Eosinophilia in Patients with Eosinophilic Pneumonia

Katoh

Nobumoto

Matsumoto

et al. 2010

“…Eosinophils are multifunctional leukocytes implicated in the pathogenesis of various inflammatory processes, including allergic diseases, bronchial asthma, chronic rhinosinusitis (CRS), helminth and viral infections, tumor immunity, and tissue injury [1,2,3]. The mere presence of eosinophils, as in the normal intestinal mucosa [4], does not lead to pathology.…”

Section: How Are Eosinophils Activated To Release Proinflammatory Andmentioning

confidence: 99%

Human Eosinophil Innate Response to Alternaria Fungus through Protease-Activated Receptor-2

Matsuwaki

Wada

Moriyama

et al. 2011

Eosinophils are multifunctional leukocytes implicated in the pathogenesis of allergic diseases. An association between eosinophilic inflammation and infection or colonization by fungi has also been long recognized. However, the mechanisms underlying how eosinophils are activated and how they release proinflammatory and immunomodulatory mediators such as major basic protein (MBP) and eosinophil-derived neurotoxin remain largely unknown. We used a fungus, i.e. Alternaria, as a model microbe relevant to human asthma and chronic rhinosinusitis (CRS) to investigate the molecular mechanisms involved in the immune recognition of ubiquitous environmental allergens. Human eosinophils are activated by live Alternaria alternata organisms, release their granule proteins, and kill the fungi. Eosinophils, but not neutrophils, respond to secreted products from A. alternata. We found that eosinophils are equipped with innate cellular activation machinery that responds to an extracellular aspartate protease secreted by Alternaria. Aspartate protease activation of protease-activated receptor (PAR)-2 probably involves a novel mechanism different from that for serine protease activation of PAR-2. Thus, human eosinophils may recognize certain danger signals or virulence factors produced by fungi and provoke inflammatory responses against these organisms. Dysregulation of such an innate immune mechanism may be involved in the pathophysiology of certain human inflammatory diseases, including asthma and CRS.

“…Upon stimulation, they produce and release not only granule proteins and leukotrienes but also a number of cytokines and chemokines [3]. To date, 12 chemokines, consisting of GRO-A (CXCL1), ENA78 (CXCL5), IL-8 (CXCL8), MIG (CXCL9), IP-10 (CXCL10), I-TAC (CXCL11), MCP-1 (CCL2), MIP-1A (CCL3), RANTES (CCL5), MCP-3 (CCL7), eotaxin 1 (CCL11), and MCP-4 (CCL13), have been reported to be released from eosinophils [3,4]. However, these chemokines are also known to be released by other types of blood cells and tissue cells [5].…”

Section: Introductionmentioning

confidence: 99%

Human Eosinophils Produce and Release a Novel Chemokine, CCL23, in vitro

Matsumoto

Fukuda

Hashimoto

et al. 2011

Background: CCL23 (MPIF1/CK-BETA-8) is a novel CC chemokine that plays important roles in the inhibition of myeloid progenitor cell development, the selective recruitment of resting T lymphocytes and monocytes, and the potentiation of VEGF-induced proliferation and migration of human endothelial cells. Since eosinophils participate in the pathogenesis of airway remodeling, we examined CCL23 production and release by human eosinophils in vitro. Methods: Using Ficoll and antibody-coated immunomagnetic beads, eosinophils and other blood cells were purified from peripheral blood samples obtained from normal subjects and mildly allergic patients. Eosinophils were cultured in the presence of 10 ng/ml granulocyte-macrophage colony-stimulating factor (GM-CSF), 10 ng/ml IL-5, 100 ng/ml IFN-γ, 100 ng/ml IFN-α, or immobilized secretory IgA (sIgA). Total mRNA was extracted after 6 h of culture, and mRNA expression was measured using a microarray and RT-PCR. The CCL23 concentrations in the supernatants and cell lysates after 24 and 48 h of culture were measured by ELISA. Results: CCL23 mRNAs (both CK-β8-1 and CK-β8) were constitutively expressed in fresh eosinophils, and their expression levels were higher than in other types of blood cells. CCL23 mRNAs were significantly increased by stimulation with GM-CSF and IL-5 and slightly by IFN-α and immobilized sIgA. Fresh eosinophils contained trace amounts of CCL23 protein. CCL23 was significantly released into the supernatant when the eosinophils were stimulated with GM-CSF or IL-5 but not with IFN-γ or immobilized sIgA. Conclusion: Our data suggest that eosinophils produce and release CCL23 and may be involved in some in vivo physiological and pathological conditions.