|Wyman, T - UNV COLO SCHOOL OF MED|
|Bjornsen, A - UNV COLO SCHOOL OF MED|
|Elzi, D - UNV COLO SCHOOL OF MED|
|SMITH, C. WAYNE|
|England, K - UNV COLO SCHOOL OF MED|
|Kelher, M - UNV COLO SCHOOL OF MED|
|Silliman, C - UNV COLO SCHOOL OF MED|
Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 19, 2002
Publication Date: July 24, 2002
Citation: WYMAN, T.H., BJORNSEN, A.J., ELZI, D.J., SMITH, W.C., ENGLAND, K.M., KELHER, M., SILLIMAN, C.C. A TWO-INSULT IN VIVO MODEL OF PMN-MEDIATED PULMONARY ENDOTHELIAL DAMAGE: REQUIREMENTS FOR ADHERENCE AND CHEMOKINE RELEASE. AMERICAN JOURNAL OF PHYSIOLOGY. 2002. 283:C1592-C1603. Interpretive Summary: This paper shows that white blood cells called neutrophils are primed to cause tissue injury by certain toxins that are present in considerable amounts in the gastrointestinal track.
Technical Abstract: Lysophosphatidylcholines (lyso-PCs), generated during blood storage, are etiologic in a two-insult, sepsis-based model of transfusion-related acute lung injury (TRALI). Individually, endotoxin (LPS) and lyso-PCs prime but do not activate neutrophils (PMNs). We hypothesized that priming of PMNs alters their reactivity such that a second priming agent causes PMN activation and endothelial cell damage. PMNs were primed or not with LPS and then treated with lyso-PCs, and oxidase activation and elastase release were measured. For coculture experiments, activation of human pulmonary microvascular endothelial cells (HMVECs) was assessed by ICAM-1 expression and chemokine release. HMVECs were stimulated or not with LPS, PMNs were added, cells were incubated with lyso-PCs, and the number of viable HMVECs was counted. Lyso-PCs activated LPS-primed PMNs. HMVEC activation resulted in increased ICAM-1 and release of ENA-78, GRO alpha, and IL-8. PMN-mediated HMVEC damage was dependent on LPS activation of HMVECs, chemokine release, PMN adhesion, and lyso-PC activation of the oxidase. In conclusion, sequential exposure of PMNs to priming agents activates the microbicidal arsenal, and PMN-mediated HMVEC damage was the result of two insults: HMVEC activation and PMN oxidase assembly.