Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(TNF alpha)-induced sequestration of neutrophils (PMN) in lungs and of the resultant PMN-dependent pulmonary edema. Guinea pig lungs perfused with Ringers-albumin were challenged with TNF alpha (1,000 U/ml) for 90 min, followed by addition of fresh perfusate containing 2 x 10(7) human PMN. TNF alpha challenge caused sequestration of PMN in the pulmonary vascular bed as indicated by a threefold increase in lung tissue myeloperoxidase activity (MPO). The activation of the sequestered PMN with phorbol 12-myristate 13-acetate (PMA; 5 x 10(-9) M) produced threefold increases in pulmonary artery (Ppa) and pulmonary capillary hydrostatic (Pcap) pressures, and twofold increases in lung wet-to-dry weight (W/D) ratio and capillary filtration coefficient (Kf,c) over baseline. TNF alpha prestimulation was required for these responses since activation of PMN with PMA in control lungs produced smaller increases in Ppa and Pcap (P less than 0.01) and did not change the W/D and Kf,c. TNF alpha prestimulation also induced the expression of intercellular adhesion molecule (ICAM-1) on pulmonary vascular endothelial cells. Monoclonal antibodies (mAbs) to the neutrophil CD18 integrin (beta-chain of CD11/CD18 complex) (mAb IB4) and to its endothelial cell ligand ICAM-1 (mAb RR1/1) were used to examine the role of PMN adhesion in the TNF alpha-induced responses. Pretreatment of PMN with mAb IB4 prevented PMN uptake and increases in Ppa, Pcap, Kf,c, and W/D ratio. Addition of mAb RR1/1 to the perfusate reduced PMN uptake by 58%, and prevented the increases in Ppa, Pcap, Kf,c, and W/D ratio, as with mAb IB4. The findings indicate that TNF alpha prestimulation of lungs mediates PMN uptake and that this requires the expression of ICAM-1 and its interaction with CD18 integrin on PMN. The activation of PMN sequestered by ICAM-1-dependent mechanism contributes to the development of pulmonary vascular injury and edema.
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PMID:Tumor necrosis factor mediates experimental pulmonary edema by ICAM-1 and CD18-dependent mechanisms. 134 98

To study the value of indexes of endothelial cell function in experimentally induced pulmonary microvascular injury, lung damage was produced in anesthetized dogs by intravenous injection of oleic acid (OA; n = 6), alpha-naphthylthiourea (ANTU; n = 5), or phorbol myristate acetate (PMA; n = 6). Angiotensin-converting enzyme (ACE) activity in serum and simultaneous measurements of serotonin (SER) and propranolol (PROP) pulmonary extraction along with several physiologic parameters were determined and compared with those obtained in a control group (n = 5) before and then at 2-h intervals for 8 h after administration of the toxic agent. ACE activity in serum showed a sustained and significant increase in the PMA and OA groups throughout the whole study period, whereas it decreased significantly at 4 h in the ANTU group. SER pulmonary uptake decreased significantly, but slightly, only in the PMA group at 8 h (-5%). At 6 and 8 h respectively, PROP extraction dropped significantly in the PMA (-11 and -13%) and OA (-13 and -19%) groups. This decrease in PROP extraction was likely to result from physiologic changes due to the development of pulmonary edema as suggested by the correlation between the changes in amine uptake and those affecting pulmonary artery pressure and total static respiratory compliance. The lack of effects on SER uptake by the lungs under these experimental conditions indicate that dissociation exists between metabolic dysfunction of pulmonary endothelial cells and fluid leakage.
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PMID:Effects of oleic acid-, alpha-naphthylthiourea-, and phorbol myristate acetate-induced microvascular damage on indexes of pulmonary endothelial function in anesthetized dogs. 284 32

Neutrophil inhibitory factor (NIF) is a recently cloned 41-kDa protein from the canine hookworm that binds CD11b/CD18 and inhibits CD11b/CD18-dependent neutrophil adhesion. We evaluated NIF's effects on neutrophil-dependent lung injury in guinea pigs. Pulmonary vascular endothelial CD54 (ICAM-1) was induced in buffer-perfused lungs by 90-min exposure to 1000 U/ml TNF-alpha. Human neutrophils (2 x 10(7)) were added to the perfusate and activated by 5 x 10(-9) PMA; in some lungs, the neutrophils were pretreated with NIF (100 nM) before their addition to the perfusate. Lung injury was assessed by wet:dry weight ratio, and neutrophil uptake by lung myeloperoxidase (MPO) activity. HUVEC exposed to TNF-alpha for 90 min were assayed for neutrophil adhesion, and we compared PMA-stimulated neutrophil adhesion to endothelial cells and fibrinogen-coated plates. PMA-induced pulmonary edema (lung wet:dry ratio increased from 8.8 +/- 0.7 to 18.8 +/- 4.4) was inhibited by NIF (10.0 +/- 1.0). Lung MPO activity concomitantly decreased from 17.1 +/- 6.1 to 8.7 +/- 1.8 U/mg dry lung tissue in the NIF-treated group, similar to controls (6.9 +/- 2.0). Endothelial monolayer experiments confirmed that NIF reduced neutrophil adherence (basal adhesion of 11 +/- 3% increased to 30 +/- 5% with TNF-alpha pretreatment of endothelial cells, an increase that was reduced to 10 +/- 4% with NIF). Moreover, NIF prevented PMA-induced neutrophil adhesion to fibrinogen, a CD11b/CD18-dependent event, but produced a smaller decrease in adherence to endothelial cells, which also involves CD11a/CD18 integrins. These studies indicate that NIF prevents neutrophil-dependent lung vascular injury by inhibiting neutrophil adhesion to the TNF-alpha-activated endothelium.
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PMID:Neutrophil inhibitory factor prevents neutrophil-dependent lung injury. 759 91

The administration of leukotrienes (LTs) into the pulmonary circulation results in edema formation and increased vascular permeability. We reported previously that the administration of phorbol myristate acetate (PMA, 20 micrograms/kg) to intact anesthetized dogs results in a reduction in circulating white blood cells as well as the development of pulmonary edema concomitant with the appearance of LTs in the lungs. In contrast, when a smaller dose of PMA (10 micrograms/kg) was administered, neither extravascular lung water nor LTs increased, although there was a similar reduction in circulating white blood cells. In the present study, we used a property of indomethacin, namely, its capacity to augment the formation of LTs, to examine further the relationship between LT generation and pulmonary edema formation in response to PMA administration. In intact pentobarbital-anesthetized dogs pretreated with saline (N = 9), the administration of PMA at a dose of 10 micrograms/kg, i.v., did not result in any change in extravascular lung water or in LTB4 present in bronchoalveolar lavage fluid (BALF). In contrast, in six animals pretreated with indomethacin (5 mg/kg), the administration of this dose of PMA resulted in increases in both extravascular lung water (P < 0.05) and LTB4 (P < 0.05) in BALF. These results provide support for the hypothesis that leukotrienes are requisite for PMA-induced increases in extravascular lung water.
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PMID:Effect of indomethacin on increases in leukotriene B4 and pulmonary edema in response to phorbol ester administration in dogs. 809 88