Acute lung injury:apoptosis and signaling mechanisms.
Acute lung injury (ALI) has been documented clinically following several pathological states such as trauma, septic shock and pneumonia. The histopathological characteristics, paired with the production of a number of cellular pro-inflammatory mediators, play a crucial role in the progression of ALI. During ALI, polymorphonuclear neutrophil (PMN)-mediated apoptosis is delayed by macrophages, possibly via effects on the Fas/FasL mediated pathway, leading to the accumulation of these cells at the site of injury and inflammation. The transcriptional regulation of NFkappaB, CREB, and AP-1 also regulates the pathogenesis of ALI. During sepsis and septic shock, we found evidence of infiltrating leukocytes in the alveolar spaces along with an increased number of TUNEL-positive cells in the lung sections. We also observed an increased expression of TRADD and Bax/Bcl(2) ratio at 7 days post-sepsis. In contrast, the NFkappaB/IkappaB ratio increased at 1 day post-sepsis. Together, these data provide evidence illustrating the induction of apoptosis in lung tissues subsequent to the onset of polymicrobial sepsis. The results support the concept that the upregulation of apoptosis following lung inflammation plays a crucial role in the development of acute lung injury and related disorders such as ARDS.
Chopra
Mani
M
Department of Biomedical Sciences, Texas A&M Health Science Center, Baylor College of Dentistry, Dallas, TX 75246, USA.
Reuben
Jayne S
JS
Sharma
Avadhesh C
AC
D055371:Acute Lung Injury / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis / Q000502:physiology*; D016207:Cytokines / Q000502:physiology; D006801:Humans; D016676:Macrophages, Alveolar / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D018805:Sepsis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology
D016207:Cytokines; D014157:Transcription Factors