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283 Bronchial hyper-responsiveness in children with asthma correlates with mast cell but not eosinophil activation
.i ALLERGY
210 Abstracts
CLIN. IMMUNOL .IANUARY 1991
281
0 (TGF-13) + Isl; IS * ~. c. G. De-me* +Basel, Switzerland. inhibits the IL4TGF-82 strongly induced synthesis of IgE in a dosedependent but non isotype-specific manner. Kinetic studies show that TGF-5 acts mainly during the IL4dependent stage of the IgE response. The suppression is not overcome by Further exogenous IL2 and LMW-BCGF. studies suggest that TGF-0 directly acts on B cells to prevent their activation/proliferation rather than IL4-directed counteract the to It inhibits both switching to IgE. the proliferation and differentiation into IgE secreting cells of highly purified B cells stimulated with IL4, PMA and irradiated EL4 thymoma cells. In contrast, it does not influence the IgE response nor the proliferation of pure B cells costimulated with IL4 and EBV. Most interestingly, TGF-D does not suppress and may enhance the synthesis spontaneous WE by lymphocytes of allergic donors and this enhancement is associated with a decreased endogenous production of IFN-y.
283
BRONCHIAL HYPER-PESPONSIVENESSIN CIfIUXZEN WITH ASTHMA CORRELATESWITH MAST CELL BUT NOT COSIKOPHIL ACTIVATION. A.C. Ferguson, KC., M. Whitelaw, B.Sc., H. E$?own, T.L.,Vancouver, Canada Bronchial hyper-responsiveness (BAX) i? closely associated with bronchial ir.flamat;:ji which is characterized by eosinophil mfi.ltr<%tion. Eosinophils (El and mast ceiiz in;:) iii the bronchial lumen have been correlated viti~ t:ie severity of BHR but it is unclear :if ;xx, inflammatory mediators from either cc:! t:Jpe are we 1 ::creforF important as causative factors. studied 17 children aged 11 + 2.5 jr- with mild to moderately severe chronicasthna rn compare BHIi determined by PCzo Kistamine wit? the anmmt of E derived cationic protein (ECP! and X 'derived tryptase assessed by radioimmunoassay i.l: Eosinophils wen: quantabroncholavage fluid. tated by differential counts of Wright's szained cytocentrifuged slides. The rmmber of E per ml of lavaq~ fiux.u iioq transformed data) was correlated with 10:~ PCZOH The concentration of CCP 11, (IT = .444, p C.05). lavage fluid was correlated with the ~ercentagc of E (I = .478, p (.05) but not with 'log PC2oH the concentra(r = -.36:, p = NS). ;n contrast tion of tryptase was highly correla+ed mtt log PCsOH (r = -.714, p<.005). These findings confirm that BIik i;; asthmatic children is associated with E accmulation II‘ the airway. Eosinophils are unlikely t3 contribute directly to BHR however since the degree of activation of E and mediator ro:.iasc as indicated by ECP secretion is not related to t!~e level of BHR. Activation of LC and release of MC mediators, in contrast, majj "lay an in~ortar:!. role.
282
CONTROLS THE LEVEL OF INTERFERON-a INTERLEUKIN-4 mRNA IN HUMAN PERIPHERAL Deusch. M.D. BLOOD LYMPHOCYTES. Kai Classen, Franz Waaner, M.D. Meinhard M.D., and J&o Prim, M.D, Munich, FRG. it has been shown that Recently, interand interferon-gamma (IFN-g) feron-a (IFN-a) are capable to suppress IgE secretion by human peripheral blood our However, to (PBL). lymphocytes knowledge the mechanisms that regulate this phenomenon have not been fully this question, To address elucidated. we stimulated human PBL with PHA in the presence or absence of IFN-a for five of IL-4 days and analyzed the levels mRNA employing specific primers for ILIL-l-B, TNFa and TNF-IS 4, IL-2 , IL-la, chain reaction the polymerase with result of this (PCR). As a that IFN-a investigation, we found IL-4 mRNA but suppresses selectively other lymphokines that of the not the addition of Moreover, studied. IL-6, other lymphokines (IL-2. IL-l, IL-4) did not influence the PHA-induced synthesis of IL-4 mRNA. Therefore. our the notion that support the data inhibition of IgE synthesis by IFN-a is of suppression the mediated by cytoplasmic IL-4 mRNA levels. Moreover, our results emphasize the potential use of IFN-a as a therapeutic tool in the mediated by diseases treatment of increased IgE levels.
284
UPREGULATION OF GM-CSF SYNTHESIS AND RELEASE IN AS'I'NMA~.IC ~l3ROtK%lAL EPITHELIUM S:Nattoli, AND EOSIEBrbPBfL ACTIVATIaEl. M. Marini, C. Brasca, G. Ve Franchis, L. A. Fasoli. Dept.s of Medicine, Allegra, Respiratory Disease, and Nuclear Med., University of Milan, Milan, Italy. We examined the in vitro interaction between airway epithelial cells (EC) and eosinophils (EO) from 5 asthmatics by determining the effect of EO supernatant on the activation of peripheral blood ~0. The incubation of EO with the supernatant of asthmatic EC for 1 hour increased the generation of superoxide anions and the release of LTC4, triggered by PMA and calcium ionophore, by more than 2-fold. The supernatant of EC from 6 normals did not exert any significant effect. Preincubation of asthmatic EC conditioned media with anti-GM-CSF antiserumabolisled their activity and the addition of rll GMCSF restored it. The supernatants of asth matic EC contained 0.88 + 0.09 rig/ml immu noreactive GM-CSF whereas the content of isununoreactive GM-CSF in normal EC conditioned medium was 0.21 + 0.105 rig/ml (p< 0.025). EC from asthmatTc patients also expressed increased levels of GM-CSF mRNA by Northern blot analysis, when compared to normal EC. Thus, both the synthesis and release of GM-CSF by EC are upregulated in asthma and this may contribute to eosinophil activation in asthmatic airways.
s
GElOk?TyTw -OR
210 Abstracts
CLIN. IMMUNOL .IANUARY 1991
281
0 (TGF-13) + Isl; IS * ~. c. G. De-me* +Basel, Switzerland. inhibits the IL4TGF-82 strongly induced synthesis of IgE in a dosedependent but non isotype-specific manner. Kinetic studies show that TGF-5 acts mainly during the IL4dependent stage of the IgE response. The suppression is not overcome by Further exogenous IL2 and LMW-BCGF. studies suggest that TGF-0 directly acts on B cells to prevent their activation/proliferation rather than IL4-directed counteract the to It inhibits both switching to IgE. the proliferation and differentiation into IgE secreting cells of highly purified B cells stimulated with IL4, PMA and irradiated EL4 thymoma cells. In contrast, it does not influence the IgE response nor the proliferation of pure B cells costimulated with IL4 and EBV. Most interestingly, TGF-D does not suppress and may enhance the synthesis spontaneous WE by lymphocytes of allergic donors and this enhancement is associated with a decreased endogenous production of IFN-y.
283
BRONCHIAL HYPER-PESPONSIVENESSIN CIfIUXZEN WITH ASTHMA CORRELATESWITH MAST CELL BUT NOT COSIKOPHIL ACTIVATION. A.C. Ferguson, KC., M. Whitelaw, B.Sc., H. E$?own, T.L.,Vancouver, Canada Bronchial hyper-responsiveness (BAX) i? closely associated with bronchial ir.flamat;:ji which is characterized by eosinophil mfi.ltr<%tion. Eosinophils (El and mast ceiiz in;:) iii the bronchial lumen have been correlated viti~ t:ie severity of BHR but it is unclear :if ;xx, inflammatory mediators from either cc:! t:Jpe are we 1 ::creforF important as causative factors. studied 17 children aged 11 + 2.5 jr- with mild to moderately severe chronicasthna rn compare BHIi determined by PCzo Kistamine wit? the anmmt of E derived cationic protein (ECP! and X 'derived tryptase assessed by radioimmunoassay i.l: Eosinophils wen: quantabroncholavage fluid. tated by differential counts of Wright's szained cytocentrifuged slides. The rmmber of E per ml of lavaq~ fiux.u iioq transformed data) was correlated with 10:~ PCZOH The concentration of CCP 11, (IT = .444, p C.05). lavage fluid was correlated with the ~ercentagc of E (I = .478, p (.05) but not with 'log PC2oH the concentra(r = -.36:, p = NS). ;n contrast tion of tryptase was highly correla+ed mtt log PCsOH (r = -.714, p<.005). These findings confirm that BIik i;; asthmatic children is associated with E accmulation II‘ the airway. Eosinophils are unlikely t3 contribute directly to BHR however since the degree of activation of E and mediator ro:.iasc as indicated by ECP secretion is not related to t!~e level of BHR. Activation of LC and release of MC mediators, in contrast, majj "lay an in~ortar:!. role.
282
CONTROLS THE LEVEL OF INTERFERON-a INTERLEUKIN-4 mRNA IN HUMAN PERIPHERAL Deusch. M.D. BLOOD LYMPHOCYTES. Kai Classen, Franz Waaner, M.D. Meinhard M.D., and J&o Prim, M.D, Munich, FRG. it has been shown that Recently, interand interferon-gamma (IFN-g) feron-a (IFN-a) are capable to suppress IgE secretion by human peripheral blood our However, to (PBL). lymphocytes knowledge the mechanisms that regulate this phenomenon have not been fully this question, To address elucidated. we stimulated human PBL with PHA in the presence or absence of IFN-a for five of IL-4 days and analyzed the levels mRNA employing specific primers for ILIL-l-B, TNFa and TNF-IS 4, IL-2 , IL-la, chain reaction the polymerase with result of this (PCR). As a that IFN-a investigation, we found IL-4 mRNA but suppresses selectively other lymphokines that of the not the addition of Moreover, studied. IL-6, other lymphokines (IL-2. IL-l, IL-4) did not influence the PHA-induced synthesis of IL-4 mRNA. Therefore. our the notion that support the data inhibition of IgE synthesis by IFN-a is of suppression the mediated by cytoplasmic IL-4 mRNA levels. Moreover, our results emphasize the potential use of IFN-a as a therapeutic tool in the mediated by diseases treatment of increased IgE levels.
284
UPREGULATION OF GM-CSF SYNTHESIS AND RELEASE IN AS'I'NMA~.IC ~l3ROtK%lAL EPITHELIUM S:Nattoli, AND EOSIEBrbPBfL ACTIVATIaEl. M. Marini, C. Brasca, G. Ve Franchis, L. A. Fasoli. Dept.s of Medicine, Allegra, Respiratory Disease, and Nuclear Med., University of Milan, Milan, Italy. We examined the in vitro interaction between airway epithelial cells (EC) and eosinophils (EO) from 5 asthmatics by determining the effect of EO supernatant on the activation of peripheral blood ~0. The incubation of EO with the supernatant of asthmatic EC for 1 hour increased the generation of superoxide anions and the release of LTC4, triggered by PMA and calcium ionophore, by more than 2-fold. The supernatant of EC from 6 normals did not exert any significant effect. Preincubation of asthmatic EC conditioned media with anti-GM-CSF antiserumabolisled their activity and the addition of rll GMCSF restored it. The supernatants of asth matic EC contained 0.88 + 0.09 rig/ml immu noreactive GM-CSF whereas the content of isununoreactive GM-CSF in normal EC conditioned medium was 0.21 + 0.105 rig/ml (p< 0.025). EC from asthmatTc patients also expressed increased levels of GM-CSF mRNA by Northern blot analysis, when compared to normal EC. Thus, both the synthesis and release of GM-CSF by EC are upregulated in asthma and this may contribute to eosinophil activation in asthmatic airways.
s
GElOk?TyTw -OR