Regulation of CD23 in the chronic inflammatory response in asthma: a role for interferon-gamma and heat shock protein 70 in the TH2 environment.

BACKGROUND: Monocytic cells and alveolar macrophages (AMs) are activated in patients with asthma, producing inflammatory cytokines. This occurs despite a TH2 environment that consists of the cytokines interleukin (IL) 4, IL-10, and IL-13. The mechanism by which this occurs may involve cross-linking of the low-alphaffinity IgE receptor CD23. OBJECTIVE: To determine the effect of the TH2 environment with interferon-gamma (IFN-gamma) and heat shock protein 70 (HSP 70) on CD23 receptor expression and tumor necrosis factor alpha (TNF-alpha) production. METHODS: We examined the effect of IL-4 and IL-13 in culture with IFN-gamma and HSP 70 on CD23 expression in both THP-1 cells and AMs from healthy controls via flow cytometry. AMs from mild asthmatic patients and THP-1 cells were evaluated for TNF-alpha production after cross-linking CD23 with immune complexes. RESULTS: Asthmatic AMs stimulated with anti-IgE exhibited a 5.7- +/- 1.9-fold increase in TNF-alpha protein. AMs from healthy controls increased the geometric mean +/- SD of CD23 2.00- +/- 0.50-fold in IL-4 and 2.14- +/- 0.50-fold in IL-13. THP-1 cells cultured with IL-4 and IL-13 then stimulated with IFN-gamma or HSP 70 increased CD23 expression above baseline as follows: IL-4, 2.16- +/- 0.31-fold; IL-13, 2.66- +/- 0.43-fold; IFN-gamma, 2.03- +/- 0.34-fold; IL-4/IFN-gamma, 9.14- to 4.02-fold; IL-13/IFN-gamma, 11.51- +/- 5.51-fold; IL-4/HSP, 5.20- +/- 0.61-fold; and IL-13/HSP, 5.60- +/- 0.79-fold. Stimulating the CD23 receptor with immune complexes significantly increased TNF-alpha production by THP-1 cells stimulated with IFN-gamma, IL-4, IL-13, or a combination of these. CONCLUSIONS: Both IFN-gamma and HSP 70, in the TH2 environment, up-regulate CD23 expression and thus may play an important role in maintaining the chronic inflammatory state in asthma.     

Characteristics of an anti-eosinophil monoclonal antibody that recognizes granulocytes from patients with blood eosinophilia but not from subjects without eosinophilia.

To investigate cell surface antigens of activated human eosinophils using monoclonal antibodies, we established a murine anti-human eosinophil monoclonal antibody AE500 by immunizing with blood eosinophils from patients with idiopathic hypereosinophilic syndrome (HES) and characterized the reactivity to a variety of human leucocytes by a fluorescence-activated cell sorter. AE500 reacted with blood eosinophils and neutrophils in nine out of 11 patients with marked eosinophilia (greater than or equal to 2500/microliters) (seven with idiopathic eosinophilia including HES and two with asthma), but not with those in asthmatic patients with mild eosinophilia (n = 10) or in healthy subjects (n = 8). AE500 did not react with blood lymphocytes, monocytes or platelets. AE500 did not react with human myeloid or lymphoid cell lines, including eosinophilic leukemia cell lines EOL-1 and EOL-3. The reactivity of AE500 to blood eosinophils and neutrophils in patients with marked eosinophilia changed in relation to blood eosinophil counts and prednisolone therapy. In addition, the reactivity of AE500 to blood eosinophils was increased in three out of four AE500-positive eosinophils by the incubation of the cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) at 37 degrees C for 30 min, but not with interleukin 3 or interleukin-5. These results suggest that the anti-eosinophil antibody AE500 detects a cell surface antigen expressed on blood granulocytes in a hypereosinophilic state. This anti-eosinophil antibody would be useful for analysing the mechanism of eosinophilia.     

PCR analysis of the Y chromosome long arm in azoospermic patients: evidence for a second locus required for spermatogenesis

We analyzed DNA from 63 Japanese men with either azoospermiaor severe oligospermia whose Y chromosomes were cytogeneticallynormal. A total of 16 loci were examined: 15 loci on the longarm between DYS7E and DYZ1, and the YRRM1 locus, a candidategene for the azoospermic factor, AZF. One patient with a perlcentricinversion of the Y chromosome was also included. We detectedmicro-deletions in ten individuals. The YRRM1 gene was Involvedin only three of them. The remaining seven patients showed deletionbetween DYS7C and DYS239 in common, indicating the presenceof at least one additional gene, deletion of which causes azoospermia.     

Primary rhabdomyosarcoma of the iliac bone in an adult: A case mimicking fibrosarcoma

Primary rhabdomyosarcoma of bone is exceedingly rare. We present a case of rhabdomyosarcoma of the iliac bone in a 32-year-old male. Histologically, the tumour consisted mainly of a uniform proliferation of elongated spindle cells arranged in a herring bone pattern, simulating fibrosarcoma. Focally there was a conventional embryonal pattern with scattered rhabdomyoblasts possessing an eosinophilic cytoplasm. Immunohistochemical studies disclosed expression of muscle markers such as desmin and muscle-specific actin, in both the embryonal and spindle-cell areas and myoglobin only in the embryonal areas. Such histological features are unusual for classical embryonal rhabdomyosarcoma. The anatomical site and age of the patient are also atypical.     

IMMUNOHISTOCHEMICAL DEMONSTRATION OF PEPTIDE YY IN GASTROINTESTINAL ENDOCRINE TUMORS

Fourteen cases of gastrointestinal endocrine tumors were examined im-munohistochemically for peptide YY, pancreatic polypeptide, glucagon, and somatostatin. Peptide YY cells were present in seven tumors, pancreatic polypeptide cells in eight tumors, glucagon cells in six tumors, and somatostatin cells in nine tumors. All 7 rectal endocrine tumors examined were found to contain peptide YY, while in the tumors of the other sites peptide YY cells were not detected. Peptide YY cell population in the rectal tumors was small to moderate in comparison with pancreatic polypeptide and glucagon cell population. This study suggests that peptide YY cells may be a common constituent of rectal endocrine tumors together with pancreatic polypeptide and glucagon cells, and that the peptide YY spectrum of gastrointestinal endocrine tumors may be closely related to the location of the tumors. Moreover, it can also be said that peptide YY may be used as one of the markers of rectal endocrine tumors.