Group B streptococci (GBS) injure lung endothelium in vitro: GBS invasion and GBS-induced eicosanoid production is greater with microvascular than with pulmonary artery cells.

Neonatal group B streptococcal (GBS) sepsis and pneumonia cause lung endothelial cell injury. GBS invasion of the lung endothelium may be a mechanism for injury and the release of vasoactive eicosanoids. Pulmonary artery endothelial cells (PAEC) and lung microvascular endothelial cells (LMvEC) were isolated from neonatal piglets and were characterized as endothelial on the basis of morphology, uptake of acyl low-density lipoprotein, factor VIII staining, and formation of tube-like structures on Matrigel. PAEC and LMvEC monolayers were infected with COH-1 (parent GBS strain), isogenic mutants of COH-1 devoid of capsular sialic acid or all capsular polysaccharide, or a noninvasive Escherichia coli strain, DH5 alpha. Intracellular GBS were assayed by plate counting of colony-forming units resistant to incubation with extracellular antibiotics. All GBS strains invaded LMvEC significantly more than PAEC, showing that the site of lung endothelial cell origin influences invasion. DH5 alpha was not invasive in either cell type. Both isogenic mutants invaded PAEC and LMvEC more than COH-1 did, showing that GBS capsular polysaccharide attenuates invasion. Live GBS caused both LMvEC and PAEC injury as assessed by lactate dehydrogenase release; heat-killed GBS and DH5 alpha caused no significant injury. Supernatants from PAEC and LMvEC were assayed by radioimmunoassay for prostaglandin E2 (PGE2), the stable metabolite of prostacyclin (6-keto-PGF1 alpha), and the thromboxane metabolite thromoxane B2. At 4 h, live COH-1 caused no significant increases in eicosanoids from both PAEC and LMvEC. At 16 h, live COH-1, but not heat-killed COH-1, caused a significant increase in 6-keto-PGF1 alpha greater than PGE2 from LMvEC, but not PAEC. We conclude that live GBS injure and invade the lung microvascular endothelium and induce release of prostacyclin and PGE2. We postulate that GBS invasion and injury of the lung microvasculature contribute to the pathogenesis of GBS disease.