Alveolar macrophage activation after trauma-hemorrhage and sepsis is dependent on NF-kappaB and MAPK/ERK mechanisms.

Academic Article

Abstract

  • The acute respiratory distress syndrome (ARDS) is a major cause of morbidity after injury. We hypothesized that alveolar macrophage (AMPhi) chemokine and cytokine release after hemorrhage and sepsis is regulated by NF-kappaB and MAPK. Adult male rats underwent soft tissue trauma and hemorrhagic shock (~90 min) followed by crystalloid resuscitation. Sepsis was induced by cecal ligation and puncture (CLP) 20 h after resuscitation. AMPhi were harvested, and TNF-alpha, IL-6, and macrophage inflammatory protein (MIP)-2 release and serum IL-6 and TNF-alpha levels were measured at 5 h after HCLP. Lung tissues were analyzed for activation of NF-kappaB, myeloperoxidase activity, and wet/dry weight ratio. In control animals, AMPhi were stimulated with LPS with or without inhibitors of NF-kappaB and MAPK. Serum TNF-alpha and IL-6 levels and spontaneous AMPhi TNF-alpha and MIP-2 release were elevated (P < 0.05) after HCLP, concomitantly with the development of lung edema and leukocyte activation. Activation of NF-kappaB increased in lungs from the hemorrhage and CLP group compared with shams. Inhibition of NF-kappaB or the upstream MAPK significantly decreased LPS-stimulated AMPhi activation. Because enhanced release of inflammatory mediators by AMPhi may contribute to ARDS after severe trauma, inhibition of intracellular signaling pathways represents a target to attenuate organ injury under those conditions.
  • Keywords

  • Animals, Cecum, Chemokine CXCL2, Enzyme Inhibitors, Extravascular Lung Water, Flavonoids, Hemorrhage, Imidazoles, In Vitro Techniques, Interleukin-6, Lipopolysaccharides, MAP Kinase Signaling System, Macrophages, Alveolar, Male, Mitogen-Activated Protein Kinases, Monokines, NF-kappa B, Peroxidase, Pyridines, Rats, Rats, Sprague-Dawley, Respiratory Distress Syndrome, Adult, Shock, Septic, Tumor Necrosis Factor-alpha
  • Digital Object Identifier (doi)

    Author List

  • Jarrar D; Kuebler JF; Rue LW; Matalon S; Wang P; Bland KI; Chaudry IH
  • Start Page

  • L799
  • End Page

  • L805
  • Volume

  • 283
  • Issue

  • 4