ABSTRACT
Leukotriene B4 (LTB4) has been implicated in the pathogenesis of allergic diseases. BLT2, a low-affinity LTB4 receptor, is activated by LTB4 and 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT). Although the high-affinity LTB4 receptor BLT1 has been shown to exert proinflammatory roles, the role of BLT2 in allergic inflammation has not been clarified. To study the function of BLT2 in development of asthma, we used mice model of ovalbumin (OVA)-induced allergic airway disease. The 12-HHT levels were elevated in bronchoalveolar lavage (BAL) fluids of OVA-sensitized/challenged wild-type mice. BLT2-deficient mice exhibited enhanced eosinophilia in BAL fluids after OVA exposure. Interleukin (IL)-13 levels in BAL fluids and IL-13-producing CD4(+) T cells in the lungs were elevated in BLT2-deficient mice compared to wild-type mice, whereas the levels of IL-4, IL-5, and interferon (IFN)-γ in BAL fluids and serum OVA-specific IgE were comparable. Transfection of BLT2-specific small interfering RNA enhanced IL-13 production in CD4(+) T cells in vitro. Expression of BLT2 mRNA in CD4(+) T cells was significantly reduced in patients with asthma compared to healthy control subjects. These findings indicate that BLT2 has a protective role in allergic airway inflammation and that diminished BLT2 expression in CD4(+) T cells may contribute to the pathophysiology of asthma.
Subject(s)
Asthma/immunology , Eosinophilia/immunology , Lung/immunology , Receptors, Leukotriene B4/immunology , Adult , Aged , Animals , Asthma/genetics , Asthma/metabolism , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , CHO Cells , Calcium/immunology , Calcium/metabolism , Cricetinae , Cricetulus , Cytokines/immunology , Cytokines/metabolism , Eosinophilia/genetics , Eosinophilia/metabolism , Fatty Acids, Unsaturated/immunology , Fatty Acids, Unsaturated/metabolism , Humans , Leukotriene B4/immunology , Leukotriene B4/metabolism , Lung/metabolism , Lung/pathology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Middle Aged , RNA Interference , Receptors, Leukotriene B4/deficiency , Receptors, Leukotriene B4/genetics , Reverse Transcriptase Polymerase Chain Reaction , Young AdultABSTRACT
A 50-year-old man presented with visual disturbance at a local ophthalmology clinic. He was given a diagnosis of uveitis and treated with oral corticosteroids; however, his visual disturbance did not improve and he was admitted to our hospital. A chest CT scan showed a pulmonary nodule in the upper lobe of the right lung, and right hilar and mediastinal lymphadenopathy. Transbronchial biopsy yielded a diagnosis of squamous cell carcinoma, and an ophthalmologic examination revealed bilateral diffuse uveal melanocytic proliferation (BDUMP). BDUMP is a rare manifestation of paraneoplastic syndrome, and the characteristics of the condition have not yet been clarified in detail. BDUMP carries a very poor visual prognosis, and in the present case, the patient's visual disturbance progressed rapidly despite systemic chemotherapy and corticosteroid therapy.
Subject(s)
Carcinoma, Squamous Cell/pathology , Lung Neoplasms/pathology , Melanocytes/pathology , Paraneoplastic Syndromes , Uvea/pathology , Vision Disorders/etiology , Humans , Male , Middle AgedABSTRACT
We report a rare case of a thigh abscess which appeared during treatment of miliary tuberculosis. A 72-year-old woman with a history of diabetes mellitus was being treated for systemic sclerosis with prednisolone. She was then admitted to our hospital with fever, and chest computed tomography showed an abnormal shadow. She was given a diagnosis of miliary tuberculosis, and antituberculous therapy was initiated with isoniazid, rifampicin, ethambutol and pyrazinamide. Although this combination of antituberculous drugs was effective, 3 months after the initiation of treatment, a collection of fluid appeared in her left thigh. Further examination revealed the fluid to be positive for Mycobacterium tuberculosis on PCR and negative on mycobacterial culture. We thus diagnosed this phenomenon to be a paradoxical reaction.