Asthma is a chronic inflammatory disease of the lung with airflow obstruction and bronchospasm, characterized by pulmonary eosinophilia, airway remodeling, increased airway hyperresponsiveness to environmental stimuli, and excessive Th2-type cytokine production. Recent studies indicate that crosstalk between the innate and adaptive immune systems is crucial for this disease. We and others have showed that the Dok (downstream of tyrosine kinases) family adaptors, Dok-1, Dok-2, and Dok-3, play essential roles in negative regulation of a wide variety of signaling pathways in both innate and adaptive immunities. Here, histopathology and bronchoalveolar lavage fluid (BALF) cellularity showed spontaneous pulmonary inflammation in Dok-1with hallmarks of asthma, including eosinophilia, goblet cell hyperplasia, and subepithelial fibrosis. Consistently, TKO mice, but not the other mutants, showed increased airway hyperresponsiveness to methacholine inhalation. In addition, Th2-type cytokine concentrations in BALF were increased in TKO mice. These findings provide strong evidence that Dok-1, Dok-2, and Dok-3 cooperatively play critical anti-inflammatory roles in lung homeostasis.
The present report describes a rare case of spontaneous hemangiosarcoma in a nine-week-old
male Sprague-Dawley rat. At necropsy, multiple white nodules of various sizes were observed on
and within the enlarged spleen and liver and were histopathologically determined to be composed
of spindle- to oval-shaped cells that showed invasive growth without encapsulation and were
arranged solidly but partially in whorls or faint alveolar patterns with vascular-like spaces
containing small clefts or erythrocytes in the tumor mass. Immunohistochemical analysis
revealed that most of the tumor cells were strongly positive for vimentin, von Willebrand
factor (vWF) and CD34 but negative for podoplanin. In addition, electron microscopic
examination revealed the presence of Weibel-Palade bodies in the cytoplasm of the tumor cells.
Based on these findings, this case was diagnosed as a hemangiosarcoma. The splenic masses were
larger than the hepatic ones, with tumor cells mainly observed at periportal regions with tumor
embolism in the liver, suggesting that primary hemangiosarcoma initially developed in the
spleen before metastasizing.
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