leukotriene-b4 and Pneumococcal-Infections

Leukotriene A(4) hydrolase (LTA(4)H) is a proinflammatory enzyme that generates the inflammatory mediator leukotriene B(4) (LTB(4)). LTA(4)H also possesses aminopeptidase activity with unknown substrate and physiological importance; we identified the neutrophil chemoattractant proline-glycine-proline (PGP) as this physiological substrate. PGP is a biomarker for chronic obstructive pulmonary disease (COPD) and is implicated in neutrophil persistence in the lung. In acute neutrophil-driven inflammation, PGP was degraded by LTA(4)H, which facilitated the resolution of inflammation. In contrast, cigarette smoke, a major risk factor for the development of COPD, selectively inhibited LTA(4)H aminopeptidase activity, which led to the accumulation of PGP and neutrophils. These studies imply that therapeutic strategies inhibiting LTA(4)H to prevent LTB(4) generation may not reduce neutrophil recruitment because of elevated levels of PGP.

Topics: Acetylation; Animals; Bronchoalveolar Lavage Fluid; Cells, Cultured; Chemokines, CXC; Chemotaxis, Leukocyte; Epoxide Hydrolases; Female; Humans; Inflammation; Leukotriene B4; Lung; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neutrophils; Nicotiana; Oligopeptides; Orthomyxoviridae Infections; Pneumococcal Infections; Pneumonia; Proline; Pulmonary Disease, Chronic Obstructive; Smoke

Topics: Acetylation; Animals; Chemokines, CXC; Chemotaxis, Leukocyte; Epoxide Hydrolases; Humans; Inflammation; Leukotriene B4; Lung; Mice; Neutrophil Activation; Neutrophils; Nicotiana; Oligopeptides; Orthomyxoviridae Infections; Pneumococcal Infections; Pneumonia; Proline; Pulmonary Disease, Chronic Obstructive; Smoke

Exposure to pneumolysin (8.37 and 41.75 ng/ml) caused a calcium-dependent increase in the generation of prostaglandin E(2) and leukotriene B(4) by both resting and chemoattractant-activated human neutrophils in vitro. These interactions of pneumolysin with neutrophils may result in dysregulation of inflammatory responses during pneumococcal infection.

Topics: Adult; Bacterial Proteins; Dinoprostone; Humans; Leukotriene B4; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Pneumococcal Infections; Streptolysins

Human immunodeficiency virus (HIV)-infected patients are at increased risk of contracting bacterial infections, mainly pneumonia. Despite this, little is known about immunopathogenic mechanisms in HIV-related bacterial pneumonia. This paper investigates the presence of the neutrophil chemotactic mediators, interleukin-8 (IL_8) and leukotriene B4 (LTB4), in bronchoalveolar lavage (BAL) fluid from 27 HIV-infected patients with bacterial pneumonia. Significantly elevated levels of IL-8 were found in BAL fluid of patients with bacterial pneumonia [529 pg ml-1 (296-1161 pg ml-1)] compared to matched patients with Pneumocystis carinii pneumonia (PCP) [59 pg ml-1 (42-254 pg ml-1)] and healthy controls [58 pg ml-1 (37-82 pg ml-1)]. Levels of LTB4 were not elevated during bacterial pneumonia when compared to PCP patients and healthy controls. Furthermore, a positive correlation was found between IL-8 levels in BAL fluid and relative BAL neutrophilia (r = 0.60, P = 0.001) in bacterial pneumonia. In conclusion, elevated IL-8 levels in BAL fluid were found in patients suffering from bacterial pneumonia, which may account for the influx of neutrophils to the lung, whereas LTB4 appears not to be an important chemotactic factor in this setting.

Topics: Bronchoalveolar Lavage Fluid; CD4 Lymphocyte Count; Chemotaxis, Leukocyte; Haemophilus Infections; HIV Infections; Humans; Interleukin-8; Leukotriene B4; Neutrophils; Pneumococcal Infections; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Staphylococcal Infections

The concentrations of four arachidonic acid metabolites, prostaglandin E2, 6-keto-prostaglandin F1 alpha, leukotriene B4, and leukotriene C4, were measured in middle ear fluid of chinchillas 6 to 72 hours after middle ear inoculation of log-phase, heat-killed encapsulated Streptococcus pneumoniae organisms. Compared with saline-inoculated ears, significant increases in the mean concentrations of all four metabolites were observed in the pneumococcus-inoculated ears 24 hours after inoculation, but not after 6, 48, or 72 hours. Since pneumococcus inoculation caused an influx of inflammatory cells as early as 6 hours after inoculation, before the increase in arachidonate metabolites, the initial stimulus for inflammatory cell chemotaxis is probably not metabolic products of arachidonic acid such as leukotriene B4. These metabolites may, however, amplify the subsequent inflammatory response.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Chinchilla; Dinoprostone; Leukotriene B4; Otitis Media with Effusion; Pneumococcal Infections; SRS-A; Time Factors