Instructions from the vascular system - directing neural stem cell fate in health and disease.

The vascular system distributes oxygen and nutrients to all tissues in the body. Additionally, the vascular system also functions in hosting and instructing tissue-specific stem and progenitor cells. Both cell- or blood-derived signals from the vascular system regulate stem cell properties in health and disease. Studies in animal models and in human disease have begun to uncover that signals from the vascular system are not merely maintaining the stem cell niche, but also instruct stem cells for repair mechanisms outside their niche. The present article focuses on recent findings about cell- or blood-derived factors in the vascular system supporting stem cell niche maintenance or activation for tissue homeostasis and repair. We highlight the fact that certain aspects of vascular - stem cell communication are conserved between stem cell niches in different tissues. Within this context, we will especially emphasize on a potential role of the altered vascular system after CNS disease in instructing stem cell fate. Understanding the communication between the vascular system and neural stem cells might support the development for new therapeutic approaches for CNS disease.

Fibrinogen signal transduction as a mediator and therapeutic target in inflammation: lessons from multiple sclerosis.

The blood protein fibrinogen as a ligand for integrin and non-integrin receptors functions as the molecular nexus of coagulation, inflammation and immunity. Studies in animal models and in human disease have demonstrated that extravascular fibrinogen that is deposited in tissues upon vascular rupture is not merely a marker, but a mediator of diseases with an inflammatory component, such as rheumatoid arthritis, multiple sclerosis, sepsis, myocardial infarction and bacterial infection. The present article focuses on the recent discoveries of specific cellular targets and receptors for fibrinogen within tissues that have extended the role of fibrinogen from a coagulation factor to a regulator of inflammation and immunity. Fibrinogen has the potential for selective drug targeting that would target its proinflammatory properties without affecting its beneficial effects in hemostasis, since it interacts with different receptors to mediate blood coagulation and inflammation. Strategies to target receptors for fibrinogen and fibrin within the tissue microenvironment could reveal selective and disease-specific agents for therapeutic intervention in a variety of human diseases associated with fibrin deposition.

Liver-type fatty acid binding protein in serum and broncho-alveolar lavage in a model of acute respiratory failure because of surfactant depletion--a possible marker for lung damage?

INTRODUCTION: Liver-type fatty acid binding proteins (L-FABP) have been shown to be present in alveolar macrophages and type II pneumocytes of the lung. This study determined levels of L-FABP in serum and broncho-alveolar lavage (BAL) during experimental acute respiratory failure (ARF) to evaluate whether this molecule can serve as a marker for lung damage. METHODS: Male Sprague-Dawley rats (n = 24) were ventilated and either lung lavaged or lavaged and treated with surfactant, and compared to ventilated, non-lavaged controls. Blood samples were drawn every hour for 4 h to measure L-FABP concentrations in serum. At the end of the experiment a BAL was performed to determine L-FABP levels in BAL fluid. L-FABP was measured with a sandwich enzyme-linked immunosorbent assays. RESULTS: Serum L-FABP concentrations rose significantly during the first 2 h of ventilation in all groups compared with baseline values. After 2 h L-FABP levels were significantly higher in lavaged animals compared with the ventilated controls and to animals treated with surfactant. After 4 h of ventilation, L-FABP in BAL was significantly higher in lavaged, non-surfactant treated animals compared with the ventilated controls. CONCLUSION: In the early phase of experimental ARF serum L-FABP levels correlate well with the degree of lung injury.