thromboxane-b2 and Pneumonia--Pneumococcal

Polymorphonuclear leukocyte (PMN)-mediated acute lung injury from ischemia/reperfusion (I/R) remains a major cause of morbidity and mortality in critical care medicine. Here, we report that inhaled low-dose carbon monoxide (CO) and intravenous resolvin D1 (RvD1) in mice each reduced PMN-mediated acute lung injury from I/R. Inhaled CO (125-250 ppm) and RvD1 (250-500 ng) each reduced PMN lung infiltration and gave additive lung protection. In mouse whole blood, CO and RvD1 attenuated PMN-platelet aggregates, reducing leukotrienes (LTs) and thromboxane B2 (TxB2) in I/R lungs. With human whole blood, CO (125-250 ppm) decreased PMN-platelet aggregates, expression of adhesion molecules, and cysteinyl LTs, as well as TxB2. RvD1 (1-100 nM) also dose dependently reduced platelet activating factor-stimulated PMN-platelet aggregates in human whole blood. In nonhuman primate (baboon) lung infection with Streptococcus pneumoniae, inhaled CO reduced urinary cysteinyl LTs. These results demonstrate lung protection by low-dose inhaled CO as well as RvD1 that each reduced PMN-mediated acute tissue injury, PMN-platelet interactions, and production of both cysteinyl LTs and TxB2. Together they suggest a potential therapeutic role of low-dose inhaled CO in organ protection, as demonstrated using mouse I/R-initiated lung injury, baboon infections, and human whole blood.

Topics: Acute Lung Injury; Animals; Antimetabolites; Carbon Monoxide; Cell Communication; Docosahexaenoic Acids; Female; Humans; Leukocytes, Mononuclear; Leukotrienes; Lung; Male; Mice; Papio; Pneumonia, Pneumococcal; Streptococcus pneumoniae; Thromboxane B2

To study the pathogenic mechanism underlying intestinal injury in the aged rat with pneumonia.. The model of rats with pneumococcus pneumonia was reproduced, and animals were divided into young control group (YCG), young model group (YMG), aged control group (ACG) and aged model group (AMG). The pathological change of lung tissue and intestine, contents of intestinal 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), thromboxane B(2) (TXB(2)), nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) activity were determined in various groups.. The lung and intestinal injury in AMG was more serious than that in the YMG. The decreases in SOD activity and 6-keto-PGF(1alpha) content, the increases in contents of TXB(2), NO, MDA in the YMG and the AMG were obvious than those in the YCG and the ACG respectively. The decrease in SOD activity and increase in MDA content were obvious in the ACG than those in the YCG. In addition, the decrease in SOD activity and increase in MDA content in the AMG were significant compared with those in the YMG.. The Prostaglandin metabolism and the free radical injury might be in the pathogenesis of intestinal injury in the aged rats with pneumonia. The intestinal injury induced by free radical in aged rats with pneumonia appears to be more obvious with ageing.

Topics: 6-Ketoprostaglandin F1 alpha; Aging; Animals; Free Radicals; Intestinal Mucosa; Lung; Male; Malondialdehyde; Nitric Oxide; Pneumonia, Pneumococcal; Prostaglandins; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Thromboxane B2

Eicosanoid production during phagocytosis of pyogenic bacteria by rabbit alveolar macrophages was studied as a model of early events in the pathogenesis of pneumonia. Adherent alveolar macrophages, prelabelled with [3H]-arachidonic acid (AA), were incubated with live, opsonized Staphylococcus aureus or Pseudomonas aeruginosa (bacteria:macrophage ratio of 50:1) at 37 degrees C for 90 min. Supernatant eicosanoids were extracted and separated by reverse phase high performance liquid chromatography (RP-HPLC). While the amounts of labelled PGE2, TXB2, and PGD2 produced in response to the two organisms were equal, the amount of PGF2 alpha elicited by S. aureus amounted to three times that released during macrophage challenge with P. aeruginosa. Overall, preferential release of cyclooxygenase products occurred during phagocytosis of S. aureus. In contrast, eicosanoids identified presumptively as oxygenated metabolites of AA predominated in cultures challenged with opsonized P. aeruginosa. Live, non-opsonized P. aeruginosa elicited the same profile of eicosanoids, but in reduced amounts. Inhibitor studies indicated that these AA derivatives were not synthesized via the macrophage lipoxygenase pathway. Their production was dependent on the viability of P. aeruginosa. Macrophages challenged with opsonized, heat-killed P. aeruginosa resulted in production of an eicosanoid profile similar to that elicited by S. aureus. Secondary metabolism by P. aeruginosa of eicosanoids released from the macrophage did not contribute to the unique profile produced during the interaction of this organism with labelled macrophages. Our data indicate that during binding to macrophages, the primary human pathogen, P. aeruginosa, specifically modulates the profile of eicosanoids produced. This effect on inflammatory mediators may be of biological significance in the pathogenesis of pneumonia.

Topics: Animals; Female; Macrophages; Phagocytosis; Pneumonia, Pneumococcal; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Pseudomonas aeruginosa; Rabbits; Species Specificity; Staphylococcus aureus; Thromboxane B2

We compared the effects of high frequency jet ventilation (HFV), conventional ventilation (CMV), and spontaneous breathing (SB) on regional pulmonary blood flows (QLLL), standard cardiopulmonary measurements and the serum levels of the first generation metabolites of prostacyclin (6-keto-PGF1 alpha) and thromboxane A2 (TxB2) in established left lower lobe pseudomonas aeruginosa pneumonia in 11 sheep. Gram negative pneumonia resulted in significant increases in alveolar-arterial oxygen gradients [(A-a)DO2] and pulmonary shunt fractions (Qs/Qt), as well as a significant decrease in QLLL during SB. Significant differences in standard haemodynamics, (A-a)DO2, Qs/Qt, and QLLL were not observed when HFV was compared to CMV. However, serum levels of 6-keto-PGF1 alpha were elevated when the animals underwent HFV. We conclude that HFV is a safe and efficient method of oxygenation and ventilation in unilobar gram negative pneumonia and also results in a significant increase in the serum levels of 6-keto-PGF1 alpha when compared to CMV in sheep. The exact significance of the latter finding is the subject of current investigation.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Cardiac Output; Female; Hemodynamics; Pneumonia, Pneumococcal; Pseudomonas Infections; Pulmonary Circulation; Respiration; Respiration, Artificial; Sheep; Thromboxane B2