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.     

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.     

Exercise for Healthy Lungs

Indian Journal of Pediatrics -     

Instituting a Curriculum for Cardio-Obstetrics Subspecialty Fellowship Training

Maternal mortality is rising in the United States, and cardiovascular disease is the leading cause. Adverse pregnancy outcomes such as preeclampsia and gestational diabetes heighten the risk of cardiovascular complications during pregnancy and the peripartum period and are associated with long-term cardiovascular risks. The field of cardio-obstetrics is a subspecialty within adult cardiology that focuses on the management of women with or at high risk for heart disease who are considering pregnancy or have become pregnant. There is growing recognition of the need for more specialists with dedicated expertise in cardio-obstetrics to improve the cardiovascular care of this high-risk patient population. Current recommendations for cardiovascular fellowship training programs accredited by the Accreditation Council for Graduate Medical Education involve establishing core competency in the knowledge of managing heart disease in pregnancy. However, little granular detail is available of what such training should entail, which can lead to knowledge gaps. Additionally, dedicated advanced subspecialty training in this area is not commonly offered. Multidisciplinary collaborative teams have been shown to improve outcomes in cardiac patients during pregnancy, and cardiovascular fellows-in-training interested in cardio-obstetrics should have the opportunity to participate in and contribute to a pregnancy heart team. In this document, we describe a proposed specialized cardio-obstetrics training pathway that could serve to adequately prepare trainees to competently and comprehensively care for women with cardiovascular disease before, during, and after pregnancy.