Cytokine responses to group B streptococci induce nitric oxide production in respiratory epithelial cells.
Streptococcus agalactiae (group B streptococcus [GBS]) is a leading cause of neonatal pneumonia, sepsis, and meningitis. Early-onset GBS pneumonia is characterized by marked pulmonary epithelial and endothelial cell injury. Innate proinflammatory responses to GBS infection that may contribute to the respiratory pathology include the synthesis and release of cytokines, prostaglandins, and nitric oxide (NO). The hypothesis that NO is directly induced in lung epithelial cells by invading GBS or indirectly induced by cytokines released by GBS-infected mononuclear cells was tested. A549 transformed human respiratory epithelial cells were directly cultured with GBS, cocultured with GBS-infected human mononuclear cells or purified macrophages, or exposed to conditioned culture medium from human mononuclear cells infected by GBS. The culture medium of A549 cultures was assayed for NO secretion, and the cell lysates were tested for presence of inducible nitric oxide synthase (iNOS) mRNA by reverse transcriptase PCR (RT-PCR). GBS-treated A549 cells neither secreted detectable NO nor expressed iNOS mRNA. GBS interaction with human mononuclear cells, however, stimulated release of soluble factors that readily induced iNOS mRNA expression and NO secretion by A549 cells. Inflammatory mediator-induced nitric oxide (NO) production by alveolar epithelium may exceed that of other lung cell types such as macrophages, and induction during GBS infection may play a significant role in pulmonary defense or free-radical-mediated lung injury.
Goodrum
Kenneth J
KJ
Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701-2979, USA. goodrum@ohio.edu
Poulson-Dunlap
Jane
J
D002461:Cell Line, Transformed; D002478:Cells, Cultured; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology; D015870:Gene Expression; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D013292:Streptococcus agalactiae / Q000276:immunology* / Q000502:physiology
D016209:Interleukin-8; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II