HYPEROXIA INDUCES PLATELET ACTIVATION AND LUNG SEQUESTRATION - AN EVENT DEPENDENT ON TUMOR-NECROSIS-FACTOR-ALPHA AND CD11A

Mice were exposed to pure oxygen for various times to explore the pulm onary platelet trapping associated with alveolar damage, its mechanism , and its role in the lesions. Platelet sequestration, evaluated by el ectron microscopy and by injection of radiolabeled platelets, was dete ctable after 72 h and reached a maximum after 96 h of exposure (i.e., shortly before death). Circulating platelets (analyzed by Facscan) sho wed some increase in the expression of CD11a and CD62, but little chan ge in CD31 and CD61. Both platelet activation and lung sequestration w ere dependent on TNF-alpha, since antibody against TNF-alpha reduced t he expression of CD11a on circulating platelets and their sequestratio n in the lung. Lung platelet sequestration was also decreased by anti- CD11a MoAb. Northern blot analysis of lung mRNA isolated at 96 h of ox ygen exposure revealed a 7-fold increase in CD54 (intercellular adhesi on molecule-1 [ICAM-1]) and a 2.5-fold increase in TNF-alpha mRNAs res pectively. These results demonstrate that the platelet pulmonary trapp ing induced by hyperoxia is dependent upon TNF-alpha and the CD11a-CD5 4 adhesion molecules. However, platelet trapping does not appear to pl ay an important pathogenic role in acute oxygen injury, since treatmen ts that decrease trapping (anti-TNF-alpha, anti-CD11a, or antibody-ind uced thrombocytopenia) did not markedly attenuate the alveolar damage.