| Acute lung injury (ALI), a syndrome of pulmonary inflammation characterized by alveolar-capillary increased permeability, is a serious complication of patients with critical illnesses, results from a variety of clinical reasons such as sepsis, shock and trauma and even leads to adult respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). Recently considerable progress has been made in the understanding and therapy of ARDS and MODS, while their mortality is still very high (40~60%). Prompt and significant solutions are required. Lipopolysaccharide on the outer membrane of gram-negative bacterial cell wall is one of the main reasons leading to systemic inflammatory response syndrome (SIRS), ALI and ARDS, during which the lung is the target organ to be involved frequently and early. Polymorphonuclear neutrophils (PMNs) provide the first line of the natural immune system to defend against invaders. However, PMNs are principal cellular mediators in acute inflammatory response induced by gram-negative bacteria. It is widely believed that inappropriate PMN accumulation in the lung and over-activation with prolonged life-span play an important role in the pathogenesis of the deteriorative way, systemic inflammatory response syndrome (SIRS)-ALI-ARDS^MODS. So to remove the unwanted, excessively activated PMNs is key to dominate the development and prognosis of inflammation, which will throw light on the therapy of SIRS, ALI and ARDS.Cells die by passing through two processes, apoptosis or necrosis. Apoptosis is known as cell suicide regulated by various genes. From1990s the research of apoptosis has become a forward area of life science and has formed a high tide nearly involving every field of biological medicine.PMNs are terminally differentiated cells and have a very short life-span. The physiological mechanism to remove aged PMNs is the uptake of spontaneously apoptotic PMNs by marcrophages without inflammatory response so that the PMN numbers in circulation remain unchanged. Under the condition of inflammation or trauma, the life-span of PMNs can be prolonged once they enter infected sites for their constitutive apoptotic pathway is delayed by the action of local inflammatory mediators. Dysregulated PMN apoptosis in inflamed sites can result in PMN excessive accumulation, over-activation and continuous release of toxic contents, which will worsen the inflammation response. The role of PMN apoptosis in the field of inflammatory pathophysiology is in the ascendant. Evidence has suggested that apoptotic PMNs exhibit markedly diminished ability to degranulate or generate a respiratory burst, due in part to loss of functional surface receptors. Throughout the process of apoptosis, PMN membranes remain intact preventing leakage of toxic intracellular contents. As PMNs die by means of apoptosis, they are easily cleared by macrophages. In addition, macrophages secret anti-inflammatory mediators instead of pro-inflammatory ones after ingesting apoptotic PMNs. The dynamic equilibrium between apoptosis and clearance can prevent the inflammation response and tissue injury from worsening not only by excessive PMN activation but also by secondary necrosis of apoptotic PMNs. Thus it can be seen that as the physiological clearance of PMNs, the start opportunity and degree of apoptosis is an important factor to influence the development and prognosis of ALI and other inflammatory diseases.Apoptosis is a complex process of cell active death, is influenced by many extracellular and intracellular factors and modulated precisely by various signal pathways with different functions, the relationships among which are very complicated. They influence each other in a harmoniousway to form a complex net to fulfill the precise and accurate regulation of PMN apoptosis. Understanding the parts, functions and relationships of these signal pathways is undoubtedly the significant gap to reveal the nature and manipulation of PMN apoptosis. Nuclear factor-icB (NF-icB), an important nuclear trans...
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