Nieswandt, B. and Echtenacher, B. and Wachs, F. P. and Schroeder, J. and Gessner, J. E. and Schmidt, R. E. and Grau, G. E. and Maennel, Daniela N. (1999) Acute systemic reaction and lung alterations induced by an antiplatelet integrin gpIIb IIIa antibody in mice. BLOOD, 94 (2). pp. 684-693. ISSN 0006-4971,
Full text not available from this repository. (Request a copy)Abstract
Shock is frequently accompanied by thrombocytopenia. To investigate the pathogenic role of platelets in shock, we examined the in vivo effects of monoclonal antibodies (MoAbs) against mouse platelet membrane proteins. Injection of the platelet-specific MoAb MWReg30 to the fibrinogen receptor (gpIIb/IIIa) rendered mice severely hypothermic within minutes. Isotype-matched control antibodies, even if they also recognized platelet surface antigens, did not induce comparable signs. MWReg30 induced early signs of acute lung injury with increased cellularity in the lung interstitium and rapid engorgement of alveolar septal vessels. Despite this in vivo activity, MWReg30 inhibited rather than stimulated platelet aggregation in vitro. MWReg30-binding to platelets led to phosphorylation of gpIIIa, but did not induce morphological signs of platelet activation. The MWReg30-induced reaction was abolished after treatment with MoAbs 2.4G2 to Fc gamma RII/III and was absent in Fc gamma RIII-deficient mice, clearly demonstrating the requirement for FcyRIII on involved leukocytes. Simultaneous administration of tumor necrosis factor exacerbated, whereas a tolerizing regimen of tumor necrosis factor or bacterial lipopolysaccharide completely prevented the reaction. These data suggest that platelet surface-deposited MWReg30-immune complexes lead to an acute Fc mediated reaction with pulmonary congestion and life-threatening potential that could serve as an in vivo model of acute lung injury. (C) 1999 by The American Society of Hematology.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-NECROSIS-FACTOR; PLATELET-ACTIVATING-FACTOR; NF-KAPPA-B; MAST-CELL DEGRANULATION; FC-GAMMA-RIII; MONOCLONAL-ANTIBODY; INDUCED APOPTOSIS; IMMUNE-COMPLEXES; FUSION PROTEIN; SEPTIC SHOCK; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Jan 2023 15:01 |
| Last Modified: | 24 Jan 2023 15:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/49125 |
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