Laboratory investigation; a journal of technical methods and pathology
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The products of the blood clotting reaction, eg, thrombin and fibrinopeptides, have various proinflammatory activities and are suggested to modulate inflammation. The macrophage expression of tissue factor (TF), the clotting initiator, has been shown to cause clotting in the site of the delayed-type hypersensitivity reaction, a cellular immune response. However, the mechanism of the clotting induction in humoral immune response has been insufficiently studied. ⋯ The number of TF-positive neutrophils were correlated in time with the intensity and extent of fibrin deposition that was visualized with an mAb specific for fibrin and peaked in 24 hours. Interestingly, the fibrin deposit was partially positive for an mAb specific for neutrophil elastase-digested fibrin. These results show in vivo evidence of a close relationship between neutrophils and both clotting and fibrinolysis in the Arthus reaction and may suggest that these neutrophil functions contribute to the pathogenesis of this hypersensitivity inflammation.
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The pathogenesis of cigarette smoke-induced pulmonary hypertension is not well characterized. We used RT-PCR to examine gene expression of nitric oxide synthase 2 (NOS-2), nitric oxide synthase 3 (NOS-3), endothelin, and vascular endothelial growth factor (VEGF) and its flk-1 receptor (VEGF-R) in main pulmonary arteries and in intraparenchymal arteries microdissected from alcohol-fixed paraffin blocks. The main pulmonary artery and intraparenchymal vessels responded in a similar fashion, with up-regulation of endothelin, VEGF, and VEGF-R gene expression evident by 2 hours after smoke exposure. ⋯ These findings suggest that the pulmonary vasculature very rapidly responds to cigarette smoke with up-regulation of mediators that control vascular cell proliferation and vascular constriction. These changes support the idea that pulmonary hypertension in cigarette smokers reflects a direct effect of smoke on the vasculature. The pattern of response in the vessels is distinctly different from that in the airways.