Bleomycin (BLM) has been reported to induce lung inflammation and fibrosis in human and mice and showed genetic susceptibility. Interestingly, the C57BL/6 (B6) mice had prominent mediastinal fat-associated lymphoid cluster (MFALCs) under healthy condition, and showed susceptibility to development of lung fibrosis following BLM administration. However, the pathogenesis of lung lesion progression, and their correlation with MFALC morphologies, remain to be clarified. To investigate the correlations between MFALC structures and lung injuries in B6 mice, histopathological examination of mediastinal fat tissues and lungs was examined at 7 and 21 days (d) following a single 50 μL intranasal (i.n.) instillation of either BLM sulfate (5 mg/kg) (BLM group) or phosphate-buffered saline (control group). The lung fibrosis was examined by Masson’s trichrome (MT) stain of paraffin sections and mRNA expression levels of Col1a1, Col3a1, and Acta2 in different frozen lung samples. Furthermore, immunohistochemistry for CD3, B220, Iba1, Gr1, BrdU, LYVE-1, and peripheral node addressin (PNAd) was performed to detect T- and B-cells, macrophages, granulocytes, proliferating cells, lymph vessels (LVs), and high endothelial venules (HEVs). We found that MFALCs were more abundant in the BLM group as compared to the control group. The lung of BLM group developed pneumonitis with severe cellular infiltrations at 7 days and significant collagen deposition (MT) and higher expression of Col1a1, and Col3a1 at 21 days post-administration. Numerous immune cells, proliferating cells, HEVs, and LVs were observed in both MFALCs and lungs of the BLM group. Interestingly, PNAd + HEVs were observed in the lungs of the BLM group, but not the control group. Moreover, numerous Gr1 + polymorphonuclear and mononuclear-like ring cells were found in the MFALCs and lungs of the BLM group. Interestingly, flow cytometric analysis revealed a significant increase of B-cell populations within the MFALCs of BLM group suggesting a potential proliferative induction of B-cells following inflammation. Furthermore, significant positive correlations were observed between quantitative parameters of these immune cells in both the lungs and MFALCs. Thus, we suggest a potentially important role for MFALCs and HEVs in the progression of lung disease, especially in inflammatory lung disease.

We investigated spatiotemporal changes in host tissues during foreign body reactions. Silicone tube was subcutaneously embedded into ICR mice, and tissue surrounding silicone (TSS) was observed at 2, 7, 14, 21, 28, 43, and 70 days (D) postsurgery. The thin layer (TL) and loose connective tissues (LCTs) (inside and outside the TSS) developed until D21 and densified afterward. Neutrophils infiltrated the TSS until D14 and formed neutrophil extracellular traps (NETs) in the TL during D7‐21. In the LCTs, mast cell counts increased until D21, and macrophage numbers peaked at D14. Several macrophages showed LYVE‐1 expression, supporting a tissue‐remodeling role. Developmental indices of collagen fibers (CFs) and reticular fibers (RFs) increased during D2‐21. NETs, but not neutrophils, were detected after D28. Mast cell numbers peaked at D43 and were maintained until D70. Myofibroblasts consistently localized to the TL from D14. During D21‐28, the area of connective tissue (CNT), and CFs and RFs decreased and increased, respectively, and both remained constant during D28‐70. The CF density remained constant from D21 and increased at D70. Thus, TSS showed two phases: inflammation and CNT development (D2‐21), and inflammation convergence and CNT stabilization (D28‐70). These results provide insights into foreign body reactions in clinical cases.

This study evaluated endothelial cells and podocytes, both being primary components of the glomerular filtration barrier, in the progression of membranoproliferative glomerulonephritis (MPGN) using modified scanning electron microscopy (mSEM) analysis. BXSB/MpJ-Yaa model mice exhibited autoimmune-mediated MPGN characterised by elevated serum autoantibody levels, albuminuria, renal dysfunctional parameters, and decreased glomerular endothelial fenestrations (EF) and podocyte foot process (PFP) effacement with immune cell infiltration. Similar to transmission electron microscopy, mSEM revealed a series of pathological changes in basement membrane and densities of EF and PFP in BXSB/MpJ-Yaa compared with control BXSB/MpJ at different stages. Further, immunopositive area of endothelial marker (CD34), podocyte functional molecules (Nephrin, Podocin, Synaptopodin, and Wilms’ tumour 1 (WT1)), and vascular endothelial growth factor A (VEGF A) significantly decreased in the glomerulus of BXSB/MpJ-Yaa compared with BXSB at final stage. The indices of glomerular endothelial injuries (EF density and immunopositive area of CD34 and VEGF A) and podocyte injuries (PEP density and immunopositive area of podocyte functional molecules) were also significantly correlated with each other and with indices of autoimmune disease and renal dysfunction. Thus, our results elucidated the pathological crosstalk between endothelial cells and podocytes in MPGN progression and the usefulness of mSEM for glomerular pathological analysis.

The reproductive characteristics and ovarian development in cotton rats (Sigmodon hispidus, CRs) are unclear, although CRs are commonly used as animal models in biomedical research. We previously reported that young (6–8 weeks) CRs showed multi-oocyte follicles (MOFs) and double nucleated oocytes (DNOs) in different stages of follicles. The developmental changes in neonatal CR ovaries were investigated in the present study and were compared with our findings in previous studies of unique phenotypes, particularly in oocytes. CR ovaries at postnatal days (PND) 0, 4, and 7 were obtained from the Hokkaido Institute of Public Health. Samples were analyzed by light and transmission electron microscopy. The general histology and folliculogenesis in CR ovaries were similar to those in other experimental rodents. However, DNOs were observed in all age categories and were frequently observed in primordial follicles, whereas MOFs started to develop from PND4 with greater frequency in primary follicles. Almost all developing follicles expressed DEAD (Asp-Glu-Ala-Asp) box polypeptide 4 and forkhead box L2, which are representative markers of oocytes and follicular epithelial cells, respectively. Ki-67 staining demonstrated the proliferative activity of granulosa cells, but not of oocytes, in follicles. Moreover, rapid folliculogenesis of CR due to a small number of apoptotic oocytes was suggested, based on results of the terminal deoxynucleotidyl transferase dUTP nick end labeling assay, confirming the formation of DNOs or MOFs. These findings clarify the development of unique phenotypes of neonatal CR ovaries and support it as a useful model to better understand folliculogenesis and oocytogenesis as well as their abnormalities in humans and other animals.

A histomorphological study was performed in the major lymphoid tissues (thymus, bursa of Fabricus and spleen) of the six 21-day-old indigenous ducklings of Bangladesh by H & E staining method during the period from March to May 2011. In the present study, it was observed that the thymus was enclosed by a thin connective tissue capsule. Numerous fine septa of connective tissue originated from the capsule and divided the organ into incompletely separated lobules. Each lobule organized into a peripheral cortex and a central medulla. The bursa of Fabricus was consisted of mucosal folds (plicae). Numerous follicles filled the lamina propria of each fold and each bursal follicle was composed a peripheral cortex and a central medulla. A layer of undifferentiated epithelial cells occupied the periphery of the medulla, which was separated from the cortex by a capillary layer. The darkly stained cortex was composed of many closely packed small lymphocytes. The paler medulla contained fewer cells of various sizes. The spleen was surrounded by a thick splenic capsule and there were a small number of trabeculae. The white pulp was composed of network of reticular cells and reticular fibers within various size lymphocytes and plasma cells were diffusely distributed. The red pulp of the spleen was formed from venous sinuses and anastomosing cord of reticular cells, macrophages, lymphocytes and blood cells. The length and breadth of the thymic lobules, bursal follicles and white pulp of the spleen were 226.68 and 165.78cm, 204.45 and 138.23cm, and 129.05 and 103.43cm respectively. The result of the present work revealed that the immunocompetent cells were arranged scatteredly or densely as an unorganized lymphatic nodules in the lymphoid tissues. The length and breadth of the thymic lobules were higher followed by bursal follicle and splenic white pulps were varied within the lymphoid tissues and even one another in indigenous ducklings. The results of the present study indicate that the architecture and distribution of lymphocytes and lymphoid follicles of ducklings is very close to the chicken and this study might be helpful to understand the changes in the frequency of the population of immunocompetent cells in drug induced, vitamin and mineral supplemented or hormone treated duck in future.DOI = http://dx.doi.org/10.3329/bjvm.v9i1.11212 Bangl. J. Vet. Med. (2011). 9(1): 53-58

According to our previous reports, impaired oocyte pickup was observed in the oviductal infundibulum of autoimmune disease (AD) mouse model, suggesting a relationship between female infertility and AD. This study examined the relationship between AD and infundibulum morphofunction by focusing on the epithelial cilia. Healthy MRL/MpJ and AD-prone MRL/MpJ-Fas lpr/lpr mice were examined at 3 and 6 months of age, representing early and late disease stages, respectively. Oocyte pickup indices decreased with AD progression indicated by splenomegaly, autoantibody production, and increased T-cell counts of infundibulum mucosa in MRL/MpJ-Fas lpr/lpr mice. Ciliary beating frequency (CBF) and height in the infundibulum were faster and higher in MRL/MpJ-Fas lpr/lpr mice than in MRL/MpJ mice at the early AD stages, although the absolute CBF values were lower at the late AD stage. At late stage, ciliary height did not differ between mouse lines, but the morphological index of cilia beating direction indicated randomized patterns in MRL/MpJ-Fas lpr/lpr mice. The tracheal mucosa was also examined as a representative example of cilia morphology; its CBF decreased at late AD stage in MRL/MpJ-Fas lpr/lpr , however, there were no AD-related morphological changes. Our results demonstrate altered cilia motility in systemic and reproductive organs, with such morphological changes of the infundibulum likely impairing function, including oocyte pickup .

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