Presence of pulmonary intravascular macrophages in the equine lung: some structuro-functional properties.

The pulmonary intravascular macrophages (PIMs) have been described in several species of animals. This study demonstrates for the first time that the equine lung has PIMs as resident phagocytes in its microvasculature. Their salient features such as globular surface coat, structures of the endocytic pathway, and related cell organelles closely resemble those of the calf, goat, and sheep. The exquisite organization of the coat globules in the form of a linear chain was structurally similar to the lipolytic lipase and the heparin-sensitive globular coat from PIMs of calf, goat, and sheep. Monastral blue (MB) when employed as a tracer to assess the phagocytic properties of equine PIMs induced similar modification of the globules of the coat into lipid droplets, reminiscent of neutral lipids. Lipids droplets (modified coat globules) were delivered into acid phosphatase-positive endosomes and lysosomes. Concurrently, the unaltered globules of the coat, probably internalized via fluid-phase constitutive pinocytoses, followed a different endocytic pathway. Large-scale platelet uptake by the PIMs was observed with thrombocytopenia in MB-treated ponies. The possible significance of hypothetical LDL-coat and the endocytic organelles as equivalents of synthetic apparatus of vasoactive lipids in the PIMs of horse needs to be assessed in future studies.     

Surface coat of sheep pulmonary intravascular macrophages: Reconstitution,and implication of a glycosyl-phosphatidylinositol anchor

Background: Pulmonary intravascular macrophages (PIMs) of sheep have a globular surface coat that facilitates endocytosis of tracer particles and Escherichia coli lipopolysaccharide, and is disrupted by the heparin and Brefeldin A treatments. The present study investigated the in vivo dynamics of the coat globules following heparin-mediated removal, and the mechanism of globule organization on the plasma membrane of PIMs in vitro. Methods: Sheep were administered heparin at a dose of 50 IU/kg body weight IV, and euthanised at 30 min, 3, 6, 12, 48, and 120 hr (n = 2 for each treatment) after the treatment. Control sheep (n = 2) were injected with normal saline solution. The tissues were processed for an ultrastructural examination and acid phosphatase (ACPase) cytochemistry. Heparintreated lungs were subjected to morphometric analysis of the coat globules. Lung tissues from normal sheep (n = 2) were incubated with phosphatidylinositol-specific-phospholipase C (PIPLC; 2 IU/ml PBS) in vitro for 30 and 75 min. Results: Heparin study: The ultrastructural and morphometric data showed that the coat globules were removed at 30 min and reconstituted within 48 hr of the treatment. The PIMs showed priminent Golgi complexes associated with secretory vesicles, microtubules, and centriole between 3–12 hr of heparin treatment. Acid phosphatase cytochemistry also demonstrated secretory activity in the Golgi complexes of PIMs during the coat reconstitution. PIPLC study: The coat globules of PIMs were removed in a time-dependent mode by the PIPLC treatment without damage to other cell organelles. Conclusions: This study demonstrates a time-dependent reconstitution of the coat of PIMs in conjunction with secretory activity following heparinmediated removal, probably through sequenstration of the globules from blood. This ability is of functional significance as the coat mediates particle endocytosis by the PIMs. The results also suggest the presence of a glycosyl-phosphatidylinositol (GPI) anchor in tethering of globules on the plasma membrane of PIMs to offer a structural basis for their integrity in pulmonary vascular flow. © 1995 Wiley-Liss, Inc.     

Spinal cord compression in renal osteodystrophy

Summary A patient undergoing regular haemodialysis for chronic renal insufficiency developed neck pain followed by progressive spinal cord compression due to subluxation at the level C3-4. Decompression, laminectomy and osteosynthesis led to an almost complete recovery. A review of all the histological specimens suggested that hyperparathyroidism and not amyloidosis caused the vertebral destruction.     

Neither lymphotoxin alpha nor lymphotoxin beta receptor expression is required for biogenesis of lymphoid aggregates or differentiation of natural killer cells in the pregnant mouse uterus

Gene ablation studies in mice indicate that lymphotoxin (LT)alpha, LTbeta and LTbetaR are essential for the genesis of lymph nodes (LN), normal structural development of peripheral lymphoid tissues and the differentiation of natural killer (NK) cells. LTbetaR binds to the heterotrimeric cytokines LTalpha1beta2 and LIGHT. LTs also regulate stromal cell expression of lymphocyte homing chemokines. Uterine decidualization in normal (+/+) mice is accompanied by the appearance and maturation of large numbers of uterine NK (uNK) cells that differentiate from precursors mobilized to the uterus from secondary lymphoid tissues. uNK cells accumulate in a transient, lymphocyte-rich region known as the metrial gland or, more recently, the mesometrial lymphoid aggregrate of pregnancy (MLAp). To determine if LTs contribute to development of the MLAp, and to the differentiation and/or localization of uNK cells, a histological study was undertaken of implantation sites from LTalpha null, LTbetaR null and gestation day-matched, normal mice. Implantation sites from the gene-ablated mice contained abundant numbers of uNK cells that localized appropriately. This indicates that the stromally derived molecules supporting NK cell differentiation in the uterus differ from those used in secondary lymphoid organs.     

Potential involvement of gelatinases and their inhibitors in Mannheimia haemolytica pneumonia in cattle

Mannheimia haemolytica infection of the lower respiratory tract of cattle results in a bronchofibrinous pneumonia characterized by massive cellular influx and lung tissue remodeling and scarring. Since altered levels of gelatinases and their inhibitors have been detected in a variety of inflammatory conditions and are associated with tissue remodeling, we examined the presence of gelatinases in lesional and nonlesional lung tissue obtained from calves experimentally infected with M. haemolytica. Lesional tissue had elevated levels of progelatinase A and B and active gelatinase A and B when compared with nonlesional tissue obtained from the same lung lobe. In vitro, M. haemolytica products stimulated production of gelatinase B, but not its activation, by bovine monocytes. Alveolar macrophages showed constitutive production of gelatinase B but no change in response to M. haemolytica products. Bovine neutrophils exposed to M. haemolytica products also released gelatinase B, and there was a significant increase in the activated form of this enzyme. These effects were virtually identical when recombinant O-sialoglycoprotease was used to stimulate these cells. M. haemolytica products also enhanced the expression by bovine monocytes and alveolar macrophages of the tissue inhibitor of metalloproteinase 1. Our results provide evidence that matrix metalloproteinases are activated in lung lesions from cattle with shipping fever and that M. haemolytica virulence products induce production, release, and especially activation of gelatinase B by bovine inflammatory cells in vitro.     

Accumulation of alpha-oxoaldehydes during oxidative stress: a role in cytotoxicity.

Glyoxal, methylglyoxal (MG), and 3-deoxyglucosone (3-DG) are physiological alpha-oxoaldehydes formed by lipid peroxidation, glycation, and degradation of glycolytic intermediates. They are enzymatically detoxified in cells by the cytosolic glutathione-dependent glyoxalase system (glyoxal and MG only) and by NADPH-dependent reductase and NAD(P)+-dependent dehydrogenase. In this study, the changes in the cellular and extracellular concentrations of these alpha-oxoaldehydes were investigated in murine P388D1 macrophages during necrotic cell death induced by median toxic concentrations of hydrogen peroxide and 1-chloro-2,4-dinitrobenzene (CDNB). Alpha-oxoaldehyde concentrations were determined by derivatization with 1,2-diamino-4,5-dimethoxybenzene. There were relatively small increases in cellular and extracellular glyoxal concentration, except that extracellular glyoxal was decreased with hydrogen peroxide. The cytosolic concentration of 3-DG and the cytosolic and extracellular concentrations of MG, however, increased markedly. Aminoguanidine inhibited alpha-oxoaldehyde accumulation and prevented cytotoxicity induced by hydrogen peroxide and CDNB. The accumulation of glyoxal and MG in toxicant-treated cells was a likely consequence of decreased in situ activity of glyoxalase 1. The effect was marked for MG but not for glyoxal, suggestive of a greater metabolic flux of MG formation than of glyoxal. The accumulation of 3-DG in toxicant-treated cells was probably due to the decreased availability of pyridine nucleotide cofactors for the detoxification of 3-DG. Impairment of alpha-oxoaldehyde detoxification is cytotoxic, and this may contribute to toxicity associated with GSH oxidation and S conjugation in oxidative stress and chemical toxicity, and to chronic pathogenesis associated with diabetes mellitus where there is oxidative stress and the formation of glyoxal, MG, and 3-DG is increased.     

Epidemiology and Transmission of Kaposi’s Sarcoma-Associated Herpesvirus

This review summarizes the current knowledge pertaining to Kaposi sarcoma-associated herpesvirus (KSHV) epidemiology and transmission. Since the identification of KSHV twenty years ago, it is now known to be associated with Kaposi’s sarcoma (KS), primary effusion lymphoma, and multicentric Castleman’s disease. Many studies have been conducted to understand its epidemiology and pathogenesis and their results clearly show that the worldwide distribution of KSHV is uneven. Some geographical areas, such as sub-Saharan Africa, the Mediterranean region and the Xinjiang region of China, are endemic areas, but Western Europe and United States have a low prevalence in the general population. This makes it imperative to understand the risk factors associated with acquisition of infection. KSHV can be transmitted via sexual contact and non-sexual routes, such as transfusion of contaminated blood and tissues transplants, or via saliva contact. There is now a general consensus that salivary transmission is the main route of transmission, especially in children residing in endemic areas. Therefore, there is a need to better understand the sources of transmission to young children. Additionally, lack of animal models to study transmission, gold standard serological assay and the lack of emphasis on endemic KS research has hampered the efforts to further delineate KSHV transmission in order to design effective prevention strategies.