RGD Reference Report - Platelet-activating factor potentiates protamine-induced lung edema. Role of eicosanoids. - Rat Genome Database

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Platelet-activating factor potentiates protamine-induced lung edema. Role of eicosanoids.

Authors: Chen, CR  Voelkel, NF  Chang, SW 
Citation: Chen CR, etal., Am J Respir Crit Care Med. 1994 Jan;149(1):34-40.
RGD ID: 4890432
Pubmed: PMID:8111595   (View Abstract at PubMed)
DOI: DOI:10.1164/ajrccm.149.1.8111595   (Journal Full-text)

Platelet-activating factor (PAF) is a cell membrane-derived ether lipid that plays an important role in acute lung vascular injury. We recently reported that PAF potentiates protamine-induced lung edema by enhancing pulmonary venoconstriction. As PAF is known to stimulate lung eicosanoid synthesis, we investigated the role of peptidoleukotrienes and other eicosanoids in this priming effect of PAF. Addition of PAF (1.6 nM), followed 10 min later by protamine (50 micrograms/ml), to perfusate of salt solution-perfused rat lungs resulted in marked arterial and venous constrictions and severe lung edema. Lung tissue thromboxane B2, 6-ketoprostaglandin F1 alpha and leukotriene C4 (LTC4) were markedly elevated 20 min after PAF/protamine. Pretreatment of the lungs with AA-861, a specific 5-lipoxygenase inhibitor, blocked PAF/protamine-induced leukotriene synthesis, arterial and venous constrictions, and lung edema. In addition, injection of LTC4 (1 microgram) markedly potentiated protamine-induced arterial and venous constrictions and caused lung edema similar to PAF/protamine. Indomethacin, a specific cyclooxygenase inhibitor, also reduced the vasoconstrictive and edemagenic responses to PAF/protamine. However, the pulmonary edema after LTC4/protamine was not blocked by indomethacin. In separate experiments, infusion of this "priming" dose of PAF into isolated perfused lungs induced LTC4 synthesis and augmented lung thromboxane A2 synthesis after arachidonic acid infusion. We conclude that both cyclooxygenase and lipoxygenase products of arachidonic acid metabolism are involved in PAF-induced potentiation of protamine lung edema.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pulmonary edema  ISOAlox5 (Rattus norvegicus)4890432; 4890432 RGD 
pulmonary edema  IMP 4890432 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Alox5  (arachidonate 5-lipoxygenase)

Genes (Mus musculus)
Alox5  (arachidonate 5-lipoxygenase)

Genes (Homo sapiens)
ALOX5  (arachidonate 5-lipoxygenase)


Additional Information