ABSTRACT
Suplatast tosilate (IPD), a new dimethylsulfonium agent, is used therapeutically in allergic diseases. Suplatast has been reported to attenuate airway hyperresponsiveness in guinea pigs, human IgE synthesis, and murine peritoneal eosinophilia. However, the effect of suplatast on human eosinophils is not known. In this study, we examined the effects of suplatast in human eosinophils on platelet activating factor (PAF, 1 microM)-induced chemotaxis by the blind well chamber technique, eosinophil adhesion to TNF-alpha (10 ng/ml) or IL-4 (10 ng/ml)-stimulated human umbilical vein endothelial cells (HUVECs), and expression of very late antigen-4 (VLA-4) on eosinophils and vascular cell adhesion molecule-1 (VCAM-1) on HUVECs by flow cytometry. Suplatast suppressed IL-4-induced eosinophil adhesion to HUVECs in a dose-dependent manner. Eosinophils from the normal subjects did not express VLA-4. However, there was a significant increase (P < 0.01) in the basal expression of VLA-4 in allergic patients. PAF or IL-4 did not enhance VLA-4 expression on eosinophils, and there was no significant effect of suplatast on VLA-4 expression in allergic patients. Suplatast did not affect TNF-alpha-induced VCAM-1 expression. Interestingly, suplatast significantly suppressed IL-4 induced VCAM-1 expression on HUVECs and PAF-induced eosinophil chemotaxis. These data suggest that suplatast may modify eosinophil participation in airway inflammation by attenuating inflammatory mediators-induced chemotaxis and adhesion to endothelial cells, and thus might be useful in the treatment of bronchial asthma.
Subject(s)
Anti-Allergic Agents/pharmacology , Arylsulfonates/pharmacology , Eosinophils/drug effects , Sulfonium Compounds/pharmacology , Asthma/blood , Asthma/complications , Asthma/immunology , Cell Adhesion/drug effects , Cells, Cultured/drug effects , Cells, Cultured/metabolism , Chemotaxis, Leukocyte/drug effects , Dose-Response Relationship, Drug , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Eosinophils/physiology , Gene Expression Regulation/drug effects , Humans , Integrin alpha4beta1 , Integrins/biosynthesis , Integrins/genetics , Interleukin-4/pharmacology , Platelet Activating Factor/pharmacology , Pulmonary Eosinophilia/etiology , Pulmonary Eosinophilia/prevention & control , Receptors, Lymphocyte Homing/biosynthesis , Receptors, Lymphocyte Homing/genetics , Respiratory Hypersensitivity/blood , Respiratory Hypersensitivity/complications , Respiratory Hypersensitivity/immunology , Tumor Necrosis Factor-alpha/pharmacology , Vascular Cell Adhesion Molecule-1/biosynthesis , Vascular Cell Adhesion Molecule-1/geneticsABSTRACT
We report herein an unusual case of primary malignant fibrous histiocytoma (MFH) of the ascending colon. A 47-year-old man was admitted to our hospital for further investigations following the discovery of a mass in the right lower quadrant of the abdomen during a medical checkup. Abdominal ultrasonography (US) and computed tomography (CT) demonstrated a mass extending to the right lateral side from the ascending colon. At laparotomy, a tumor was found originating in the ascending colon and infiltrating the right lateral peritoneum. A right hemicolectomy and partial peritoneal dissection were performed followed by an ileotransverse colostomy reconstruction. The resected specimen contained a tumor measuring 7 x 5 x 4 cm, the cut surface of which was yellowish white, and the mucosa of the colon was intact. Based on histological and immunohistochemical inspection, the tumor was diagnosed as MFH of the ascending colon. We reviewed the total 18 known cases of colorectal MFH documented in the literature including our case. After surgery, 4 of 17 patients died of local recurrence, all within 42 months, indicating that early and complete excision of tumor is essential to achieve cure.
Subject(s)
Colonic Neoplasms/pathology , Histiocytoma, Benign Fibrous/secondary , Peritoneal Neoplasms/secondary , Abdomen/diagnostic imaging , Colonic Neoplasms/surgery , Colorectal Surgery , Histiocytoma, Benign Fibrous/surgery , Humans , Laparotomy , Male , Middle Aged , Neoplasm Invasiveness , Peritoneal Neoplasms/surgery , Radiography, Abdominal , Tomography, X-Ray Computed , UltrasonographyABSTRACT
Human blood basophils selectively express Fc gamma RII (CDw32) among IgG receptor subtypes, but its functional role in allergic reactions remains unknown. Using the human basophilic leukemia cell line KU812F as a model system, we investigated cellular signaling events mediated through IgG receptor stimulation. KU812F cells express Fc gamma RII on their surface. mRNAs for both Fc gamma RIIA and IIB subtypes were detected by reverse transcriptase-PCR analysis. In this cell line, Fc gamma RII stimulation induced mobilization of free intracellular calcium and actin polymerization. Yet, no significant histamine release was observed, nor did blood basophils stimulated by anti-Fc gamma RII monoclonal antibody IV.3 and by a secondary antibody release histamine. These data indicate that Fc gamma RII stimulation induces cellular signaling events such as calcium mobilization in human basophils. However, these events do not lead to histamine release.
Subject(s)
Basophils/metabolism , Calcium/metabolism , Histamine Release , Receptors, IgG/physiology , Signal Transduction , Actins/metabolism , Base Sequence , Cell Line , Cells, Cultured , DNA Primers/chemistry , Electrophoresis, Agar Gel , Humans , Immunophenotyping , Molecular Sequence Data , Neutrophils/metabolism , Oligonucleotide Probes/chemistry , Polymerase Chain Reaction , RNA, Messenger/analysisABSTRACT
To clarify the role of basophils in the pathogenesis of allergic disease, we developed a new method for performing surface phenotyping of these cells in centrifugation-enriched mononuclear cell fraction. This method identified basophils on the basic of a negative reactivity with mixed FITC-conjugated monoclonal anti-bodies (mAbs) (anti-CD2, -CD14, -CD16, and -CD19) with analysis performed by flow cytometry. The validity of this approach was confirmed by sorting experiments. Various PE-conjugated mAbs were also used to examine binding to FITC-negative basophils. Basophils from asthmatic patients (n = 14) as well as from normal subjects (n = 6) were shown to express CDw32 (Fc gamma RII), CD25 (IL-2R), but not CD64 (Fc gamma RI). We also detected binding of IgG1 and IgG4 to basophils. This method of phenotyping was very rapid and simple. It thus appears to be useful in the study of allergic disease, as well as of the biology of the basophil.
