ABSTRACT
The aim of this study is to investigate the histamine-releasing ability of mast cells from asthmatic bronchoalveolar lavage fluid (BALF). Following the measurement of the forced expiratory volume at the first second (FEV1), 29 mild asthmatics were included in the study and were subjected to fibreoptic bronchoscopy. The cells recovered from the BALF were challenged with anti-IgE, calcium ionophore A23187 (CI) or adenosine, and the released histamine was measured with an enzyme-linked chromogenic assay. Enzymatically dispersed mast cells from human lung or colon tissues were employed as control groups. The results showed that mast cells from BALF were at least 100 fold more sensitive to anti-IgE than those from lung or colon tissues. However, there was little difference between mast cells from BALF, lung or colon tissues in response to CI. Adenosine failed to stimulate histamine release from BALF mast cells. In conclusion, asthmatic BALF mast cells are much more sensitive to IgE-dependent stimulation than the non-IgE-dependent ones, indicating that mast cells may play a role in the pathogenesis of asthma.
Subject(s)
Adenosine/administration & dosage , Adult , Antibodies, Anti-Idiotypic/administration & dosage , Asthma/immunology , Bronchoalveolar Lavage Fluid/cytology , Bronchoscopes , Calcimycin/administration & dosage , Colon/cytology , Dose-Response Relationship, Immunologic , Female , Forced Expiratory Volume/drug effects , Histamine Release/drug effects , Humans , Immunoglobulin E/drug effects , Ionophores/administration & dosage , Lung/cytology , Male , Mast Cells/drug effects , Middle Aged , Sensitivity and Specificity , Severity of Illness Index , Vasodilator Agents/administration & dosageABSTRACT
Ehrlich tumor expresses the ganglioside GT1b. The plasma of mice with Ehrlich ascites tumor burden also contains GT1b. The structural identity of plasma GT1b was ascertained by a series of enzymatic degradation and mass spectral analysis. Mice were vaccinated with purified plasma GT1b admixed with Freund's adjuvant (FA). Sixty nine percent suppression of Ehrlich ascites tumor growth was observed in vaccinated mice. The suppression was dose-dependent. It is hypothesized that the tumor growth-suppression is a result of immune response to GT1b Humoral immune response to GT1b was demonstrated by passive hemagglutination assay of the sera of vaccinated mice. To test the hypothesis, the mice were administered with rabbit polyclonal anti-GT1b IgM antibody in varying doses and challenged with Ehrlich tumor. A significant reduction in tumor growth (65%) was observed in mice administered with anti-GT1b IgM antibody. Again, the suppression was dose-dependent. To verify further, another batch of mice was immunized with anti-idiotypic antibodies to rabbit anti-GT1b IgM raised in rat. The polyclonal anti-idiotype antibody is expected to carry the structural image of GT1b. In a dose-dependent manner, a maximum of 82% suppression of tumor growth was observed in mice immunized with the anti-idiotype antibody. This observation further strengthened the hypothesis that ganglioside mediated suppression of tumor growth may be a result of immunogenicity of the target ganglioside. This was also supported by positive reaction of the sera of anti-idiotype vaccinated mice with both anti-idiotype antibody and ganglioside GT1b in passive hemagglutination assay. The results favour the therapeutic potential of immunogenic tumor-associated gangliosides.