Factors larger than 100 kd in post-hemorrhagic shock mesenteric lymph are toxic for endothelial cells.
BACKGROUND
Post-shock mesenteric lymph kills and injures endothelial cells (ECs), but neither the mechanism nor the mediators of lymph's toxic effect are known. Thus, in these studies we investigated and characterized potential factors that may be involved in lymph's toxic effect on ECs.


METHODS
Lymph was collected hourly from rats before shock, during the shock period, and for 6 hours post-shock and processed in several ways-including removal of cellular elements, freezing, heating, or separation by molecular weight-after which they were tested for toxicity (lactate dehydrogenase as a marker of cell injury and trypan blue as a marker of cell viability).


RESULTS
Controls consisting of medium, pre-shock lymph, and post-shock portal vein plasma had no EC toxicity. Lymph collected 1 to 3 hours post-shock resulted in the death of 90% to 95% of ECs and caused an 8- to 10-fold increase in lactate dehydrogenase release; however, this toxic effect waned by 4 hours post-shock. Endotoxin neutralization and immune cell removal did not decrease lymph cytotoxicity but complement inactivation did. By fractionating the toxic lymph samples by size, it appears that the putative EC cytotoxic mediator(s) is larger than 100,000 d.


CONCLUSIONS
Mesenteric lymph collected 1 to 3 hours after hemorrhagic shock is toxic to ECs, but this effect is lost by 4- to 5-hours post-shock and is not dependent on the presence of immune cells or endotoxin but does involve complement and other putative mediators of greater than 100,000 d.
Adams
C A
CA
Department of Surgery, UMD-New Jersey Medical School, Newark, NJ 07103, USA.
Xu
D Z
DZ
Lu
Q
Q
Deitch
E A
EA
D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000502:physiology; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008196:Lymph / Q000737:chemistry* / Q000502:physiology*; D008643:Mesentery / Q000503:physiopathology*; D008970:Molecular Weight; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D013997:Time Factors
D003165:Complement System Proteins; D007770:L-Lactate Dehydrogenase