Although AT is an important natural anticoagulant, it might attenuate inflammatory responses by inhibiting the production of TNF-a. TNF-a is capable of inducing micro-circulatory disturbance leading to various organ failures by activating neutrophils and by inducing microthrombus formation. Since microthrombus formation further increases TNF-a production to form a vicious cycle in the progression of microcirculatory disturbance, inhibition of both neu-trophil activation and microthrombus formation by AT through promotion of endothelial production of PGI2 and inherent anticoagulant activity might be important in improving microcirculatory disturbance. Because of these important properties, AT should be an useful therapeutic agent for microcirculatory disturbance in various disease states.
Activated neutrophils: Neutrophils activated by various agonists such as pro-inflammatory cytokines and release neutrophil proteases and oxygen radicals that are capable of damaging endothelial cells.
Antithrombin: One of natural anti-coagulants inhibiting coagulation factors with serine protease properties.
Calcitonin-gene related peptide: A neuropeptide synthesized in dorsal root ganglion cells and released from sensory neurons on activation.
Capsaicin-sensitive sensory neurons: Nociceptive neurons that are activated by a wide variety of noxious physical stimuli and have roles in regulation of local inflammatory responses.
Endothelial cell injury: Damage of endothelial cells induced by of noxious substances such as neutrophil elastase and oxygen free radicals and leads to impairment of the endothelial function to maintain proper microcirculation.
Prostacyclin: One of prostaglandins synthesized in endothelial cells and has potent anti-platelet, vasodilatory and anti-inflammatory activities.
Tumor necrosis factor-a: One of pro-inflammatory cytokines produced by circulating monocytes and macrophages in response to endotoxin and a representative causal substance for coagulation abnormalities and organ failures observed in sepsis.
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Dr. Okajima is Professor of the Department of Biodefense and Chief Investigator of the vascular biology research group. He contributed much to the elucidation of molecular mechanism(s) in the important linkage between the coagulation and inflammation. His work is supported by grants from the Japanese Ministry of Education, Cultures, Sports, Science and Technology and by the departmental funds of Kumamoto University in which he worked before.
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