ovalbumin and Emphysema

Cell-based therapies with embryonic or adult stem cells, including induced pluripotent stem cells, have emerged as potential novel approaches for several devastating and otherwise incurable lung diseases, including emphysema, pulmonary fibrosis, pulmonary hypertension, and the acute respiratory distress syndrome. Although initial studies suggested engraftment of exogenously administered stem cells in lung, this is now generally felt to be a rare occurrence of uncertain physiologic significance. However, more recent studies have demonstrated paracrine effects of administered cells, including stimulation of angiogenesis and modulation of local inflammatory and immune responses in mouse lung disease models. Based on these studies and on safety and initial efficacy data from trials of adult stem cells in other diseases, groundbreaking clinical trials of cell-based therapy have been initiated for pulmonary hypertension and for chronic obstructive pulmonary disease. In parallel, the identity and role of endogenous lung progenitor cells in development and in repair from injury and potential contribution as lung cancer stem cells continue to be elucidated. Most recently, novel bioengineering approaches have been applied to develop functional lung tissue ex vivo. Advances in each of these areas will be described in this review with particular reference to animal models.

Topics: Animals; Asthma; Bioengineering; Cell- and Tissue-Based Therapy; Disease Models, Animal; Embryonic Stem Cells; Emphysema; Humans; Hypertension, Pulmonary; Lung; Lung Diseases; Mice; Ovalbumin; Pulmonary Fibrosis; Regeneration; Respiratory Distress Syndrome; Stem Cell Transplantation; Stem Cells

The effects of smoking on asthma pathogenesis are complex and not well studied. We have shown recently that 3 weeks of smoking attenuates ovalbumin (OVA)-induced airway inflammation in mice and that 4-6 months of smoking induces emphysema in mice without airway inflammation. Effects of combined long-term smoking and OVA exposure have not been investigated so far.. To study whether long-term smoking affects progression of allergic airway inflammation and/or enhances the development of emphysema in mice.. Mice were sensitized to OVA and challenged with saline or OVA aerosols for 6 months. From 2 months onwards, mice were also exposed to air or smoke. Lung tissue was analysed for extent of inflammation, emphysema, remodelling and for cytokine levels, and serum for OVA-specific IgE levels.. Chronic OVA exposure of 6 months resulted in a T helper type 2 (Th2)-type inflammation with increased levels of IL-4, IL-5, IL-6 and infiltration of eosinophils, CD4(+) T cells, macrophages and plasma cells. Smoking induced a Th17-type of airway inflammation, characterized by neutrophils, macrophages, B cells and increased levels of IL-17, IL-6, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor and monocyte chemoattractant protein-1. Concomittant smoking and OVA exposure resulted in inflammation similar to OVA exposure alone. OVA exposure increased IgE levels compared with saline exposure, and smoking did not further increase these levels.. We did not find evidence for increased inflammation, IgE levels or emphysema in mice with allergic airway inflammation after 4 months of smoking compared with non-smoking. However, a 4-month exposure to smoke alone did enhance neutrophilic airway inflammation characterized by high pulmonary IL-17 levels. A Th2 inflammatory environment due to OVA exposure may be one explanation as to why no further detrimental effects of smoking on allergic airway inflammation were found.

Topics: Animals; Cell Proliferation; Cytokines; Emphysema; Immunoglobulin E; Leukocyte Count; Macrophages; Male; Mice; Mice, Inbred C57BL; Neutrophils; Ovalbumin; Pneumonia; Smoke; Time Factors

Topics: Amidines; Anaphylaxis; Animals; Dextrans; Emphysema; Female; Guinea Pigs; Hematocrit; Histamine; Histamine Release; Immune Sera; Immunization; Male; Ovalbumin; Peptides; Pyridines; Tachyphylaxis; Toxins, Biological

Topics: Anaphylaxis; Animals; Cardiovascular Diseases; Desensitization, Immunologic; Dextrans; Emphysema; Guinea Pigs; Histamine H1 Antagonists; Immune Sera; Ovalbumin; Tachyphylaxis