Protective effect of Galectin-9 in murine model of lung emphysema: Involvement of neutrophil migration and MMP-9 production.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and pulmonary emphysema. Persistent inflammation and remodeling of the lungs and airways result in reduced lung function and a lower quality of life. Galectin (Gal)-9 plays a crucial role as an immune modulator in various diseases. However, its role in the pathogenesis of pulmonary emphysema is unknown. This study investigates whether Gal-9 is involved in pulmonary inflammation and changes in emphysema in a porcine pancreatic elastase (PPE)-induced emphysema model. MATERIALS AND METHODS: Gal-9 was administered to mice subcutaneously once daily from 1 day before PPE instillation to day 5. During the development of emphysema, lung tissue and bronchoalveolar lavage fluid (BALF) were collected. Histological and cytological findings, concentrations of chemokines and matrix metalloproteinases (MMPs) in the BALF, and the influence of Gal-9 treatment on neutrophils were analyzed. RESULTS: Gal-9 suppressed the pathological changes of PPE-induced emphysema. The mean linear intercept (Lm) of Gal-9-treated emphysema mice was significantly lower than that of PBS-treated emphysema mice (66.1 ± 3.3 µm vs. 118.8 ± 14.8 µm, respectively; p < 0.01). Gal-9 decreased the number of neutrophils and levels of MMP-9, MMP-2 and tissue inhibitor of metalloproteinases (TIMP)-1 in the BALF. The number of neutrophils in the BALF correlated significantly with MMPs levels. Interestingly, Gal-9 pretreatment in vitro inhibited the chemotactic activity of neutrophils and MMP-9 production from neutrophils. Furthermore, in Gal-9-deficient mice, PPE-induced emphysema progressed significantly compared with that in wild-type (WT) mice (108.7 ± 6.58 µm vs. 77.19 ± 6.97 µm, respectively; p < 0.01). CONCLUSIONS: These results suggest that Gal-9 protects PPE-induced inflammation and emphysema by inhibiting the infiltration of neutrophils and decreasing MMPs levels. Exogenous Gal-9 could be a potential therapeutic agent for COPD.

Favorable outcome with hemoperfusion of polymyxin B-immobilized fiber column for rapidly progressive interstitial pneumonia associated with clinically amyopathic dermatomyositis: report of three cases.

We present 3 cases of rapidly progressive interstitial pneumonia (RPIP) associated with clinically amyopathic dermatomyositis (C-ADM) that were treated with two courses of direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP). Despite initial treatment with high-dose corticosteroids, pulsed cyclophosphamide, and cyclosporine, the lung disease and hypoxemia deteriorated in all the patients. After PMX-DHP treatment, the PaO2/FiO2 ratio and serum LDH and KL-6 were improved, the abnormal shadows in chest high-resolution computed tomography (HRCT) scans gradually decreased, and, finally, all patients survived. These findings indicate that PMX-DHP treatment could be effective in the management of RPIP in patients with C-ADM in combination with conventional therapy.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2006)].

From October 2006 to September 2007, we collected the specimen from 356 patients with lower respiratory tract infections in 14 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 414 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, 407 strains were examined. The isolated bacteria were: Staphylococcus aureus 64, Streptococcus pneumoniae 96, Haemophilus influenzae 87, Pseudomonas aeruginosa (non-mucoid) 52, P. aeruginosa (mucoid) 11, Klebsiella pneumoniae 20, and Moraxella catarrhalis 44. Of 64 S. aureus strains, those with 2 microg/ml or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 microg/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 27 (42.2%) and 37 (57.8%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 microg/ml or less. Against MRSA, vancomycin and linezolid showed the most potent activity and inhibited the growth of all the strains at 1 microg/ml. Carbapenems showed the most potent activities against S. pneumoniae and in particular, panipenem inhibited the growth of all the strains at 0.063 microg/ml or less. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.125 and 0.5 microg/ml, respectively. In contrast, there were high-resistant strains (MIC: over 128 microg/ml) for erythromycin (45.8%) and clindamycin (20.8%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 microg/ml or less. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and its MIC90 was 0.5 microg/ml. Against P. aeruginosa (non-mucoid), tobramycin had the most potent activity and its MIC90 was 2 microg/ml. Against K. pneumoniae, cefozopran was the most potent activity and inhibited the growth of all the strains at 0.063 microg/ml or less. Also, all the antibacterial agents except ampicillin generally showed a potent activity against M. catarrhalis and the MIC90 of them were 2 microg/ml or less. The approximately half the number (50.6%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 49.2% and 28.1% of all the respiratory infections, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. pneumoniae (29.2%), S. aureus (20.8%), and H. influenzae (12.9%). H. influenzae (25.0%) and P. aeruginosa (21.7%) also were frequently isolated from the patients with chronic bronchitis. Before the antibacterial agent administration, the bacteria frequently isolated from the patients were S. pneumoniae (27.5%) and H. influenzae (22.5%). The bacteria frequently isolated from the patients treated with macrolides was P. aeruginosa, and its isolation frequently was 39.4%.

FDG-PET and chemotherapy for successful diagnosis and treatment of cardiac metastasis from non-small cell lung cancer.

Non-small cell lung cancer was metastasized at the septal side of right atrium in 59-year-old woman who had undergone surgery for lung cancer 11 years ago. The cardiac metastasis was found by whole-body 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT), and cytologically confirmed by myocardial aspiration biopsy with right heart catheterization. The patient was treated with 4 cycles of carboplatin/pemetrexed followed by maintenance therapy with pemetrexed. The metastatic cardiac tumor shrank, and the atrioventricular (AV) block in ECG was improved. In this case, FDG-PET and chemotherapy were valuable for diagnosis and treatment of cardiac metastasis from non-small cell lung cancer.

[A case of Epstein-Barr virus-positive diffuse large B-cell lymphoma in an elderly person with a necrotizing pulmonary bulky mass].

A 52-year-old man presented with a pulmonary bulky mass, fever and cough. Chest CT showed a necrotizing bulky mass 10 cm in diameter in the right lung lower lobe. Transbronchial biopsy and CT-guided biopsy of the tumor and endobronchial ultrasound-guided transbronchial needle aspiration of the right hilar lymph node did not yield a definitive diagnosis, but the histological findings showed necrosis. We performed CT-guided biopsy of the part of the lesion where a high uptake of FDG-PET was observed. The histological diagnosis was diffuse large B-cell lymphoma. The immunohistochemical findings were positive for Epstein-Barr virus (EBV). Because the patient was more than 50 years old and had no underlying diseases, he was given a diagnosis of EBV-positive diffuse large B-cell lymphoma of an elderly patient. The pulmonary manifestation of this disease as a bulky tumor is extremely rare. In spite of the presence of a bulky pulmonary tumor, the EBV-positive diffuse large B-cell lymphoma contained necrotizing tissue, and it was difficult to obtain tissue specimens for histological examination.

Galectin-9 attenuates acute lung injury by expanding CD14- plasmacytoid dendritic cell-like macrophages.

RATIONALE: Galectin (Gal)-9 plays a crucial role in the modulation of innate and adaptive immunity. OBJECTIVES: To investigate whether Gal-9 plays a role in a murine acute lung injury (ALI) model. METHODS: C57BL/6 mice were pretreated with Gal-9 by subcutaneous injection 24 and 48 hours before intranasal LPS inoculation. MEASUREMENTS AND MAIN RESULTS: Gal-9 suppressed pathological changes of ALI induced by LPS. Gal-9 reduced levels of proinflammatory cytokines and chemokines, such as tumor necrosis factor (TNF)-α, IL-1ß, IL-6, and keratinocyte-derived cytokine; decreased neutrophils; and increased IL-10 and CD11b(+)Gr-1(+) macrophages in the bronchoalveolar lavage fluid of ALI mice. In Gal-9-deficient mice, pathological changes of ALI were exaggerated, and the number of neutrophils and the TNF-α level were increased. CD11b(+)Gr-1(+) cells were increased in the spleen of both Gal-9-treated and phosphate-buffered saline (PBS)-treated ALI mice, but only Gal-9 increased the ability of CCR2-expressing macrophages to migrate toward monocyte chemoattractant protein-1. Transfer of CD11b(+)Gr-1(+) macrophages obtained from Gal-9-treated mice ameliorated ALI. CD11b(+)Gr-1(+) macrophages obtained from Gal-9-treated but not PBS-treated mice suppressed TNF-α and keratinocyte-derived cytokine production from LPS-stimulated macrophages, and down-regulated Toll-like receptor-4 (TLR4) and TLR2 expression on thioglycollate-elicited macrophages. Fluorescence-activated cell-sorting analysis revealed that CD14 is negligible on CD11b(+)Gr-1(+) macrophages obtained from Gal-9-treated mice, although those from both groups resembled plasmacytoid dendritic cells (pDCs). Gal-9 down-regulated CD14 on pDC-like macrophages from PBS-treated mice independently of Gal-9/Tim-3 (T-cell immunoglobulin- and mucin domain-containing molecule-3) interaction, resulting in the acquisition of suppressive function, suggesting that the loss of CD14 by Gal-9 is critical for the suppression of pDC-like macrophages. CONCLUSIONS: Gal-9 attenuates ALI by expanding CD14(-)CD11b(+)Gr-1(+) pDC-like macrophages by preferentially suppressing macrophage functions to release proinflammatory cytokines through TLR4 and TLR2 down-regulation.

[A case of stage IIIB pulmonary pleomorphic carcinoma that responded well to chemoradiotherapy and surgery].

A 44-year-old man was admitted because he had a mass in the right upper lung field showing high uptake of FDG-PET. Although he had already received video-assisted thoracic surgery to remove the mass in another hospital, the procedure had been unsuccessful because of severe adhesion to the superior vena cava. The pathological diagnosis of a specimen obtained in surgery was pleomorphic carcinoma, clinical stage IIIb (c-T4N2M0). We performed concurrent chemoradiotherapy consisting of systemic chemotherapy twice with both cisplatin and vinorelbine, and radiation therapy (60Gy). The tumor size reduced by 46% immediately after chemoradiotherapy. Because there was still no evidence of distant metastasis, we performed a right upper lobectomy and resection of the superior vena cava to remove the tumor completely. We did not detect any microscopic cancer cells in the surgical specimens and the pathological diagnosis was complete response (CR). It is thought that chemotherapy and radiotherapy are ineffective for pulmonary pleomorphic carcinoma. However, in this case, concurrent chemoradiotherapy with surgical therapy was highly effective and no recurrence has been observed 13 months after surgery.

[A case of AIDS with Pneumocystis jirovecii pneumonia which required differentiation from ANCA-related lung disease].

A 41-year-old man with fever, diarrhea and skin rash received a diagnosis of drug-induced lupus. He was given corticosteroids for 3 months and was subsequently admitted to a local hospital due to dyspnea. Pneumonia was then diagnosed and he was given a new quinolone antibacterial agent. Despite this treatment, his symptoms and signs gradually worsened and he was referred to our hospital. High resolution CT (HRCT) of the chest showed diffuse ground-glass opacities, reticular shadows, parenchymal abnormalities, traction bronchiectasis, a subpleural curvilinear shadow and septal lines. Serological examinations were positive for anti-myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) and subsequent HRCT findings were consistent with ANCA-related lung disease. However, the patient had complications such as previous syphilis infection, oral candidiasis, herpes zoster, hepatitis B virus and cytomegalovirus infection. Additionally, his serum was positive for HIV antibody and HIV-1 RNA, and therefore we diagnosed AIDS. His bronchoalveolar lavage fluid revealed Pneumocystis jirovecii. It is known that HIV infection is associated with many types of autoantibodies including MPO-ANCA. Therefore, in HIV/AIDS patients with interstitial lung diseases, it is important to differentiate opportunistic Pneumocystis pneumonia infection from collagen vascular disease-associated interstitial lung diseases.

[Case of osteosarcoma of the pulmonary artery].

A 49-year-old man was admitted to our hospital for an expanding tumor in the pulmonary artery. He had visited a previous hospital complaining of dyspnea on effort and had syncope 4 months before admission, and pulmonary embolism was diagnosed because enhanced chest CT showed filling defects, with calcification in the pulmonary trunk and left pulmonary artery. Despite thrombolytic and anticoagulant therapy, the filling defects grew and expanded into the extravascular portion. Additionally, CT showed multiple pulmonary nodules and a small calcified nodule in a right-sided back muscle also appeared. At our hospital, FDG-PET showed abnormal uptake in each lesion shown on CT. We then performed a CT-guided needle biopsy of the nodule of the back muscle, which was pathologically diagnosed as osteosarcoma. He was finally given a diagnosis of osteosarcoma of the pulmonary artery. We administered cisplatin and doxorubicin with partial inhibitory effect on tumor growth. Osteosarcoma of the pulmonary artery is extremely rare, and its diagnosis is difficult before surgery or autopsy. To the best of our knowledge there have been no reports of chemotherapy for osteosarcoma of the pulmonary artery.

Galectin-9 expands immunosuppressive macrophages to ameliorate T-cell-mediated lung inflammation.

Galectin-9 (Gal-9) plays pivotal roles in the modulation of innate and adaptive immunity to suppress T-cell-mediated autoimmune models. However, it remains unclear if Gal-9 plays a suppressive role for T-cell function in non-autoimmune disease models. We assessed the effects of Gal-9 on experimental hypersensitivity pneumonitis induced by Trichosporon asahii. When Gal-9 was given subcutaneously to C57BL/6 mice at the time of challenge with T. asahii, it significantly suppressed T. asahii-induced lung inflammation, as the levels of IL-1, IL-6, IFN-gamma, and IL-17 were significantly reduced in the BALF of Gal-9-treated mice. Moreover, co-culture of anti-CD3-stimulated CD4 T cells with BALF cells harvested from Gal-9-treated mice on day 1 resulted in diminished CD4 T-cell proliferation and decreased levels of IFN-gamma and IL-17. CD11b(+)Ly-6C(high)F4/80(+) BALF Mphi expanded by Gal-9 were responsible for the suppression. We further found in vitro that Gal-9, only in the presence of T. asahii, expands CD11b(+)Ly-6C(high)F4/80(+) cells from BM cells, and the cells suppress T-cell proliferation and IFN-gamma and IL-17 production. The present results indicate that Gal-9 expands immunosuppressive CD11b(+)Ly-6C(high) Mphi to ameliorate Th1/Th17 cell-mediated hypersensitivity pneumonitis.

Galectin-9 ameliorates immune complex-induced arthritis by regulating Fc gamma R expression on macrophages.

Galectin-9 up-regulated Fc gamma RIIb expression of mouse peritoneal macrophages in vitro but down-regulated Fc gamma RIII expression. Galectin-9-treated macrophages stimulated with immune complexes (IC) produced less TNFalpha and IL-1 beta but more IL-10 than PBS-treated macrophages. Macrophage enhancing effects on IC-induced C5a and neutrophil chemotactic activity were also diminished for galectin-9-treated macrophages. In galectin-9-treated mice, the severity of IC-induced arthritis was reduced, as were pro-inflammatory cytokine levels in inflamed joints and serum C5a. Fc gamma RIIb expression of macrophages from galectin-9-treated mice was up-regulated, whereas Fc gamma RIII expression was down-regulated. Macrophages from galectin-9-treated mice produced less TNFalpha and IL-1 beta but more IL-10 than PBS-treated mice. Disease severity of galectin-9-transgenic mice was milder than wild-type mice, whereas that of galectin-9-deficient mice was exaggerated. Furthermore, macrophage Fc gamma RIIb expression in galectin-9-deficient mice was down-regulated, while Fc gamma RIII expression was up-regulated. These results suggest that galectin-9 suppresses IC-induced inflammation partly by regulating Fc gamma R expression on macrophages.

Galectin-9 accelerates transforming growth factor beta3-induced differentiation of human mesenchymal stem cells to chondrocytes.

Galectin-9 (Gal-9), a beta-galactoside binding lectin, plays a crucial role in innate and adaptive immunity. In the rat collagen-induced arthritis model, administration of Gal-9 induced repair of existing cartilage injury even when joints were already swollen with cartilage destruction. We thus attempted to explore the role of Gal-9 in chondrocyte differentiation utilizing human mesenchymal stem cell (MSC) pellet cultures. During chondrogenesis induced by transforming growth factor beta3 (TGFbeta3), MSCs strongly expressed endogenous Gal-9. Expression of Gal-9 peaked on day 14 and the neutralization of endogenous Gal-9 resulted in the reduced chondrogenesis, indicating possible involvement of Gal-9 in TGFbeta-mediated chondrogenesis. In pellets, addition of Gal-9 significantly enhanced TGFbeta3-induced chondrogenesis, as evidenced by increasing proteoglycan content, but not cell proliferation. In the absence of Gal-9, collagen expression by MSCs switched from type I to type II on 28 days after stimulation with TGFbeta3. When MSCs were co-stimulated with Gal-9, the class switch occurred on day 21. In addition, Gal-9 synergistically enhanced TGFbeta3-induced phosphorylation of Smad2, though Gal-9 did not itself induce detectable Smad2 phosphorylation. These results suggest that Gal-9 has a beneficial effect on cartilage repair in injured joints by induction of differentiation of MSCs into chondrocytes.

Galectin-9 suppresses the generation of Th17, promotes the induction of regulatory T cells, and regulates experimental autoimmune arthritis.

The effects of galectin-9 on a mouse collagen-induced arthritis (CIA) model were assessed to clarify whether galectin-9 suppresses CIA by regulating T cell immune responses. Galectin-9 suppressed CIA in a dose-dependent manner, and such suppression was observed even when treatment was started on 7 days after the booster, indicating its preventive and therapeutic effects. Galectin-9 induced the decreased levels of pro-inflammatory cytokines, IL-17, IL-12, and IFNgamma in the joint. Galectin-9 induced the decreased number of CD4(+) TIM-3(+) T cells in peripheral blood. Galectin-9-deficient mice became susceptible to CIA may be by increased number of CD4(+) TIM-3(+) T cells and decreased number of Treg cells. We further found that galectin-9 induces differentiation of naive T cells to Treg cells, and it suppresses differentiation to Th17 cells in vitro. The present results suggested that galectin-9 ameliorates CIA by suppressing the generation of Th17, promoting the induction of regulatory T cells.

Beneficial effect of galectin 9 on rheumatoid arthritis by induction of apoptosis of synovial fibroblasts.

OBJECTIVE: To compare the expression of galectin 9 (Gal-9) in synovial tissue (ST) from rheumatoid arthritis (RA) patients and osteoarthritis (OA) patients and to evaluate the effects of Gal-9 on fibroblast-like synoviocytes (FLS) in these patients. METHODS: The expression of Gal-9 in ST and FLS was compared using immunohistochemical techniques. Apoptotic cells in RA and OA ST samples were detected by TUNEL assay. Apoptosis of FLS was analyzed by the sub-G(1) method in vitro. The in vivo suppressive effects of Gal-9 on collagen-induced arthritis (CIA) in a mouse model were also elucidated. RESULTS: The percentage of Gal-9-positive cells in ST samples and the amount of Gal-9 in synovial fluid samples were significantly higher in patients with RA than in patients with OA, suggesting the involvement of Gal-9 in the development of RA. Compared with the 2 wild-type Gal-9 forms, stable Gal-9, a mutant protein resistant to proteolysis, significantly induced apoptosis of FLS from RA patients. In contrast, other galectins, such as Gal-1, Gal-3, and Gal-8, did not induce apoptosis or suppress the proliferation of human RA FLS. Stable Gal-9 preferentially induced apoptosis and suppressed the proliferation of RA FLS in vitro. It also induced apoptosis of cells in RA ST implanted into SCID mice in vivo. In a mouse model of CIA, apoptotic cells were detected in the joints of stable Gal-9-treated mice, but not phosphate buffered saline-treated mice, and suppressed CIA characterized by pannus formation with inflammatory cell infiltration and bone/cartilage destruction. CONCLUSION: Gal-9-induced apoptosis of hyperproliferative RA FLS may play a critical role in the suppression of RA.

Selective eosinophil adhesion to fibroblast via IFN-gamma-induced galectin-9.

Among galectin family members, galectin-9 was first described as a potent eosinophil chemoattractant derived from Ag-stimulated T cells. In the present study a role of galectin-9 in the interaction between eosinophils and fibroblasts was investigated using a human lung fibroblast cell line, HFL-1. RT-PCR, real-time PCR, and Western blot analyses revealed that both galectin-9 mRNA and protein in HFL-1 cells were up-regulated by IFN-gamma stimulation. On the one hand, IL-4, known as a Th2 cytokine, did not affect the galectin-9 expression in HFL-1 cells. We further confirmed that IFN-gamma up-regulated the expression of galectin-9 in primary human dermal fibroblasts. Flow cytometric analysis revealed that IFN-gamma up-regulated surface galectin-9 expression on HFL-1 cells. Stimulation of HFL-1 cells with IFN-gamma up-regulated adhesion of eosinophils, but not neutrophils, to HFL-1 cells. This adherence of eosinophils to HFL-1 cells was inhibited by both lactose and anti-galectin-9 Ab. These findings demonstrate that IFN-gamma-induced galectin-9 expression in fibroblasts mediates eosinophil adhesion to the cells, suggesting a crucial role of galectin-9 in IFN-gamma-stimulated fibroblasts as a physiological modulator at the inflammatory sites.

Association of galectin-9 with eosinophil apoptosis.

BACKGROUND: There is no information whether galectin-9 (a novel eosinophil chemoattractant) was associated with pathogenesis of eosinophilic disorders. METHODS: We assessed the expression of galectin-9 with imunostaining and in situ hybridization both in the lesion of angiolymphoid hyperplasia with eosinophilia, and peripheral blood eosinophils of eosinophilic patients (E-Eos) in comparison with those of normal volunteers (N-Eos). Regulation of expression of galectin-9 on eosinophils and the effect of galectin-9 on apoptosis of eosinophil were also evaluated. RESULTS: Many eosinophils infiltrating the site were positive for galectin-9. Surface and intracellular immunoreactive galectin-9 was more evident in E-Eos than N-Eos. When eosinophils were cultured with IL-5 in vitro, the surface galectin-9 expression of E-Eos was significantly downregulated, although that of N-Eos was not affected. Treatment of eosinophils with dexamethasone or anti-Fas antibody significantly upregulated the surface galectin-9 expression of E-Eos. In contrast, dexamethasone partially downregulated the surface galectin-9 of N-Eos, although anti-Fas antibody failed to affect on the surface galectin-9 expression. We also found that recombinant galectin-9 significantly suppressed apoptosis of E-Eos (p = 0.0431), whereas it apparently enhanced apoptosis of N-Eos (p = 0.0173). Furthermore, dexamethasone-induced apoptosis of N-Eos was significantly suppressed by galectin-9 (p = 0.0431), whereas galectin-9 failed to induce significant change in dexamethasone-induced apoptosis of E-Eos. In contrast, apoptosis induced by anti-Fas antibody in both N-Eos (p = 0.0431) and E-Eos (p = 0.0431) was enhanced by galectin-9. CONCLUSIONS: These findings suggested that galectin-9 was produced by eosinophils, and galectin-9 showed heterogeneous effects and kinetics to eosinophils, and this factor might be one of crucial factors in eosinophilic inflammation.

Two cases of Sjögren's syndrome with multiple bullae.

Here, we report two rare female cases of Sjögren's syndrome with multiple bullae, involving a 66- and a 51-year-old. Neither had any obvious pulmonary complaint. Chest radiographs and high-resolution CT (HRCT) scans showed interstitial linear and nodular opacities and multiple bullae. In the first case spirometry indicated an obstructive change judged by FEV1.0 and V50/V25. In both cases, histologic examination of the lung revealed thickening of alveolar septa and interstitial mononuclear cell infiltration. In the first case the bullae decreased in size with corticosteroid treatment. Airway narrowing due to peribronchiolar mononuclear cell infiltration causes a check-valve mechanism, which may lead to bullae formation. Although a rare occurrence, it is important to recognize that cystic or bullous lung disease can accompany Sjögren's syndrome.

Galectin-9 in physiological and pathological conditions.

We first cloned galectin-9 (Gal-9)/ecalectin as a T cell-derived eosinophil chemoattractant. Gal-9 plays a role in not only accumulation but also activation of eosinophils in experimental allergic models and human allergic patients, because Gal-9 induces eosinophil chemoattraction in vitro and in vivo and activates eosinophils in many aspects. Gal-9 requires divalent galactoside-binding activity but not the linker peptide of Gal-9 to exhibit its biological functions, and an unidentified matrix metalloproteinase is involved in the release of Gal-9. Our recent studies also showed that Gal-9 has other functions, such as cell differentiation, aggregation, adhesion, and death. Now, we and other groups are on the way of investigating the regulation and function of Gal-9 in a variety of physiological and pathological conditions. In this article, we will show the possible role of Gal-9 in physiological and pathological conditions by using our recent findings.