Blood transfusion and the two-insult model of post-injury multiple organ failure.
Neutrophils (PMNs) have been implicated in the pathogenesis of multiple organ failure (MOF). The two-insult model of MOF is based on the fundamental concept that two sequential and independent insults that are individually innocuous against the host can cause overwhelming inflammation. The in vitro PMN priming/activation sequence simulates the two-insult model. Our work has demonstrated that transfusion is an early consistent risk factor for post-injury MOF and lysophosphatidylcholines (lyso-PCs) are generated in stored blood components. Additionally, platelet-activating factor (PAF) is a key inflammatory agent produced in severely injured patients. We therefore hypothesize that two events, trauma and transfusion, enhance PMN cytotoxicity irrespective of the sequence. Superoxide (O2-) production was measured by reduction of cytochrome c, adherence to fibrinogen was assessed by the radioactivity of adherent Na2(51)CrO4 (51Cr)-labeled PMNs, and endothelial cell (EC) damage by measuring the radioactivity released from 51Cr-labeled human umbilical vein endothelial cells monolayers. Isolated PMNs were primed with buffer, PAF (2 microM), or lyso-PCs (4.5, 15, and 30 microM) followed by activation with buffer, N-formyl-methionyl-leucyl-phenylalanine (fMLP) (1 microM), PAF (2 microM), or lyso-PCs (4.5, 15, and 30 microM). Neither PAF nor lyso-PCs alone stimulated O2- production. While PAF alone caused PMN adherence, lyso-PCs alone did not allowed PMNs to adhere to fibrinogen. However, both combinations of PAF/lyso-PCs and lyso-PCs/PAF significantly augmented O2- production and PMN adherence. Furthermore, these enhanced PMN cytotoxic responses significantly caused EC damage. These findings suggest that in the scenario of the two-insult model, early or late transfusion administered following trauma can provoke PMN cytotoxicity via priming or activation, thereby increasing the risk of post-injury MOF.
Aiboshi
J
J
Department of Surgery, Denver Health Medical Center, University of Colorado Health Sciences Center, 80204, USA.
Moore
E E
EE
Ciesla
D J
DJ
Silliman
C C
CC
D001793:Blood Preservation; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000473:pathology; D005340:Fibrinogen; D006801:Humans; D007249:Inflammation; D008244:Lysophosphatidylcholines / Q000097:blood / Q000494:pharmacology; D008954:Models, Biological; D009102:Multiple Organ Failure / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D018384:Oxidative Stress; D010972:Platelet Activating Factor / Q000494:pharmacology; D012306:Risk; D013481:Superoxides / Q000378:metabolism; D065227:Transfusion Reaction
D008244:Lysophosphatidylcholines; D010972:Platelet Activating Factor; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D005340:Fibrinogen