Abstract
Chemokines, a large family of structurally related chemotactic cytokines, are essential for the migration of leukocytes during inflammatory processes. The release of neutrophil attractant chemokines such as MCP-1, Groα, ENA-78, GCP-2 and NAP-2 as well as fractalkine by lung microvascular endothelial cells (LMVEC) is dramatically increased upon stimulation with LPS. The present study was performed to investigate, whether human Lactoferrin (hLf) or Phospholipase A2-inhibitor Phosphatidylethanolamine (PE) can intervene with the release of these chemokines by LMVEC under LPS stimulation. LMVEC were protreated with hLf for various time intervals prior to stimulation with LPS or with LPS in the presence of hLf. In other experiments, cell impermeable PE, Cyclooxygenase-inhibitors (Col) (indomethacine, acetyl-salicylic acid) and a platelet activating factor (PAF)-antagonist, were added to LPS stimulated LMVEC. Chemokine release was measured by ELISA and detection of chemokine mRNA by means of RT-PCR. HLf added to LMVEC at the time of stimulation did not influence chemokine production. However, when hLf was added prior to LPS stimulation, a significant inhibition of MCP-1 (P < 0.001) and ENA-78 (P < 0.01) but not of Groα production was observed. In order to investigate if LPS induced chemokine production was dependent on PAF, Arachidonic acid (AA) or its metabolites, LMVEC were treated with PE, Col and PAF-antagonist either after or at the time of LPS stimulation. Treatment of LMVEC with PE completely inhibited the LPS induced chemokine production of MCP-1, ENA-78 and Groα in a time and dose dependent fashion. This was still observed, when LMVEC were pretreated with LPS. Col and PAF-antagonist could partly reduce LPS induced chemokine production. Furthermore mRNA expression of ENA-78, Groα, GCP-2 and fractalkine was decreased after LPS stimulation in the presence of PE. Our data demonstrate, that hLf and PE are potent agents to counteract LPS induced chemokine produktion by LMVEC. These findings may have clinical implications in the treatment of acute lung injury during sepsis.
Highlights
Ill patients requiring intensive care are at risk of iatrogenic ocular damage
Intensive Care Unit (ICU) management of critically ill patients often includes the requirement for tracheostomy and feeding access, most often a pecutaneous endoscopic gastrostomy (PEG)
Percutaneous tracheostomy is performed routinely in many medical intensive care unit (ICU) settings, in high risk surgical and trauma patients who often have unstable cervical spine injury and tissue edema, direct visualization of the cervical structures and trachea is imperative during tracheostomy
Summary
Ill patients requiring intensive care are at risk of iatrogenic ocular damage. We designed an experimental situation where external cardiac pressure conditions were controlled and adjusted to physiological extremes to mimic clinically relevant situations, while cardiac performance was assessed using left ventricular pressure–volume relationships (LVPVR) which are relatively preload and afterload independent This prospective, controlled study was undertaken to evaluate the response to therapy aimed at achieving supranormal cardiac and oxygen transport values (cardiac index >4.5 l/min/m2, oxygen delivery >600 l/min/m2, and oxygen consumption >170 l/min/m2) in patients older than 60 or with previous severe cardiorespiratory illnesses, who have undergone elective extensive ablative surgery planned for carcinoma or abdominal aortic aneurism. Whilst some human studies conducted in the critically ill and in high risk surgical patients have suggested that dopexamine may cause an increase in tonometrically measured gastric intra-mucosal pH (pHi) and an improvement in clinical outcome, this has not been confirmed in other randomised trials. In the present study the association of platelet function to inflammatory markers indicating disease severity was investigated
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