The thymus, a primary lymphoid organ and the initial site for development of T cell immunological function, is morphologically similar across species. It is actually an epithelial organ in which its epithelial cells provide a framework containing T cells as well as smaller numbers of other lymphoid cells. A symbiotic interaction exists between the thymic microenvironment and developing T cells, and the specificity of T cell release into the systemic circulation is under thymic control. The thymic cortex in a young animal is heavily populated by developing T cells along with a smaller proportion of associated epithelial cells. Larger, more mature T cells are found in the medulla where epithelial and other cell types are more abundant. Understanding normal morphological features of the thymus and their perturbations provides a cornerstone to assessing immune system function.
The thymus is a primary lymphoid organ that manifests dynamic physiological changes as animals age in addition to being exquisitely sensitive to stress and toxic insult. It is typically the first lymphoid tissue to respond to immunotoxic xenobiotics, with the first change being loss of cortical lymphocytes by apoptosis. This is followed by removal of the apoptotic cellular debris and, in the absence of recovery, may lead to loss of the cortico-medullary demarcation and organ atrophy. Nonneoplastic proliferative changes include focal lymphoid hyperplasia and proliferation of medullary epithelial cells, often with formation of ribbons, cords, or tubules. Thymomas are relatively rare tumors that exhibit a wide spectrum of morphologic types but do not metastasize. Thymic lymphomas are common in some mouse strains and can become leukemic with hematogenous spread throughout the body.
The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative changes in rats and mice. The purpose of this publication is to provide a standardized nomenclature for classifying changes observed in the hematolymphoid organs, including the bone marrow, thymus, spleen, lymph nodes, mucosa-associated lymphoid tissues, and other lymphoid tissues (serosa-associated lymphoid clusters and tertiary lymphoid structures) with color photomicrographs illustrating examples of the lesions. Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous lesions as well as lesions induced by exposure to test materials. The nomenclature for these organs is divided into 3 terminologies: descriptive, conventional, and enhanced. Three terms are listed for each diagnosis. The rationale for this approach and guidance for its application to toxicologic pathology are described in detail below.
Nicotine, a toxic tobacco component, plays an important role in the development of cardiovascular and lung diseases in smokers. Our objective was to investigate the effects of the intraperitoneal (i.p.) nicotine treatment in lung morphology. Wistar male rats (3-4 months old) were divided in five groups, a control one, and other groups treated with nicotine (1 mg/kg/day) for 8 days and sacrificed after 24, 48, 96, and 192 h. Morphometry was used to estimate the lung alveolar parenchyme and septal elastic fibers changes, and immunohistochemistry was performed to detect macrophage metalloelastase (MMP-12) and quantify vessels by immunolabelling with alpha-smooth muscle cells. Thickening of the alveolar septa was present in all nicotine groups, and associated with mononuclear cell infiltration, angiogenesis, and irregular areas of collapse. After 96 h, rat lungs showed macrophage, expressing MMP-12, that was also present after 192 h of recovery. Pleural and parenchyma inflammation, fibrosis and macrophage were also seen after 192 h. Intraperitoneal nicotine treated rats exhibited an increase of the volume fraction of alveolar parenchyme, a reduction of volume and surface fraction septal elastic fibers, and an increase of the numerical fraction of microvasculature vessels compared to control ones. MMP-12 was detected in groups of macrophages Wistar rats lung exhibited a progressive morphological damage after 192 hours of recovery, after 8 daily doses of 1 mg/kg body weight on i.p. nicotine.
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