Modulation of the release of Ang-2 in experimental endotoxic shock by a species-specific circulating factor

Abstract

ObjectivesTo study the modulation of the release of angiopoietin-2 (Ang-2) in experimental endotoxic shock. MethodsTwelve pigs were studied; eight became septic after the intravenous infusion of lipopolysaccharide (LPS) of Escherichia coli O55:B5. The concentrations of LPS, angiopoietin-2 (Ang-2), tumour necrosis factor-alpha (TNFα) and malondialdehyde (MDA) were measured soon after the LPS infusion in the serum samples from the pulmonary and systemic circulation. Peripheral blood mononuclear cells (PBMCs) were isolated from two healthy swine, from two healthy human donors and from four patients with septic shock. The PBMCs were cultured with the serum of the septic animals in the presence or absence of polymyxin B. Concentrations of Ang-2 and TNFα were measured in supernatants. ResultsSerum Ang-2 was higher in the systemic circulation than in the pulmonary circulation. Increased Ang-2 release was noted in swine PBMCs in the presence of polymyxin B. A reciprocal decrease in TNFα release was observed, typically after incubation with serum sampled from the pulmonary circulation. ConclusionThere is evidence for a circulating factor that primes Ang-2 release from blood monocytes in the event of septic shock. The finding indicates a possible site of interference within the septic shock cascade.