• Anirban Banerjee, Ernest E Moore, Nathan J McLaughlin, Luis Lee, Wilbert L Jones, Jeffrey L Johnson, Trevor L Nydam, and Christopher C Silliman.
• Department of Surgery, Denver Health Medical Center, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado 80045, USA. Anirban.Banerjee@ucdenver.edu
• Shock. 2013 Apr 1; 39 (4): 366-72.

AbstractFirm neutrophil (PMN)-endothelial (EC) adhesion is crucial to the PMN-mediated hyperinflammation observed in acute lung injury. Hypertonic saline (HTS) used for resuscitation of hemorrhagic shock has been associated with a decreased incidence of PMN-mediated lung injury/acute respiratory distress syndrome. We hypothesize that physiologically accessible hypertonic incubation (170 vs. 140 mM, osmolarity ranging from 360 to 300 mOsm/L) inhibits proinflammatory activation of human pulmonary microvascular endothelial cells (HMVECs). Proinflammatory activation of HMVECs was investigated in response to tumor necrosis factor-α (TNF-α), including interleukin 8 (IL-8) release, intercellular adhesion molecule 1 (ICAM-1) surface expression, PMN adhesion, and signaling mechanisms under both isotonic (control) and hypertonic conditions. Hyperosmolarity alone had no effect on either basal IL-8 release or ICAM-1 surface expression but did lead to concentration-dependent decreases in TNF-α-induced IL-8 release, ICAM-1 surface expression, and PMN-HMVEC adhesion. Conversely, HTS activated p38 mitogen-activated protein kinase (MAPK) and enhanced TNF-α activation of p38 MAPK. Despite this basal activation, hyperosmolar incubation attenuated TNF-α-stimulated IL-8 release and ICAM-1 surface expression and subsequent PMN adherence, while p38 MAPK inhibition did not further influence the effects of hyperosmolar conditions on ICAM-1 surface expression. In addition, TNF-α induced nuclear factor-κB DNA binding, but HTS conditions attenuated this by 31% (P < 0.01). In conclusion, HTS reduces PMN-HMVEC adhesion and TNF-α-induced proinflammatory activation of primary HMVECs via attenuation of nuclear factor-κB signaling.

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