Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested blood neutrophil functions in the patients with chronic respiratory tract diseases to study the mechanism of susceptibility to bacterial infections. Peripheral blood neutrophils were obtained from 15 healthy subjects and 14 patients including diffuse panbronchiolitis, bronchiectasis, chronic emphysema and chronic bronchitis. Seven patients suffered from the chronic P. aeruginosa infection. Firstly, neutrophil chemotaxis was determined by the method of Boyden Chamber assays using FMLP as a neutrophil chemoattractant. The number of migrated neutrophils were 239.2 +/- 65.6 cells/50 HPF in the patients group and 256.6 +/- 49.0 cells/50 HPF in the control group. Secondly, neutrophil phagocytosis against P. aeruginosa, E. coli and K. pneumoniae was determined by phagocytic activity (PA) and phagocytic index (PI). PA against each bacteria was 44.1 +/- 13.2% (P. aeruginosa), 44.8 +/- 12.3% (E. coli) and 35.8 +/- 13.6% (K. pneumoniae) in the patients group and 42.3 +/- 10.6% (P. aeruginosa), 43.0 +/- 11.9% (E. coli) and 36.3 +/- 16.0% (K. pneumoniae) in the control group. PI against each bacteria was 2.2 +/- 0.6 (P. aeruginosa), 2.1 +/- 0.3 (E. coli) and 2.6 +/- 0.9 (K. pneumoniae) in the patients group and 2.2 +/- 0.6 (P. aeruginosa), 2.2 +/- 0.4 (E. coli) and 2.5 +/- 0.6 (K. pneumoniae) in the control group. Thirdly, neutrophil bacteriocidal activity was determined by superoxide production and intracellular killing efficiency. Superoxide produced from OPZ-triggered neutrophils was 17.8 +/- 6.5 nmol/3.5 X 10(6) cells/20 min in the patients group and 20.2 +/- 5.8 nmol/3.5 X 10(6) cells/20 min in the control group, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A study of neutrophil functions in patients with chronic respiratory tract diseases]. 250 95

The possibility that polymorphonuclear leukocytes (PMN) recruited into the lung have the capability to damage alveolar septa was investigated in several strains of mice with different serum alpha 1 proteinase inhibitor levels and PMN lysosomal functions. After an intratracheal instillation of FMLP (200 micrograms), all strains of mice showed a similar PMN influx in alveolar spaces with an increase (approximately 4- to 5-fold) in bronchoalveolar lavage total cell count, which peaked at 24 to 48 hours. At this time, differential cell count in all strains revealed an approximately 40-fold increase in neutrophils. In C57BL/6J and pallid mice but not in NMRI mice, PMN influx was followed by a decrease in lung elastin content (-17% and -37%, respectively) and by the development of significant emphysema (mean linear intercept, +28% and +56%, respectively). The onset of the pulmonary lesion was preceded by a marked increase of neutrophil elastase burden in alveolar interstitium. Compared with NMRI mice, C57BL/6J and pallid mice have lower serum elastase inhibitory capacity levels. The degree of lung destruction was inversely correlated with elastase inhibitory capacity levels. Lung elastin degradation and emphysema may be induced by eliciting PMN into the lungs only in animals with a deficient anti-elastase screen. Compared with C57BL/6J mice, pallid mice showed a significantly greater lung elastin loss and a higher degree of emphysema after FMLP treatment. These differences may be accounted for by the higher baseline levels of interstitial elastase burden. It may be assumed that an enzymatically active elastase was already working on the lung interstitium before FMLP instillation in pallid mice.
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PMID:Neutrophil recruitment into the lungs is associated with increased lung elastase burden, decreased lung elastin, and emphysema in alpha 1 proteinase inhibitor-deficient mice. 876 27

Cigarette smoke (CS) is the main causative factor of chronic obstructive pulmonary disease (COPD). Current research supports the concept that airway inflammation is central to the development and progression of the disease. Studies have demonstrated that neutrophils are increased in COPD lungs and that neutrophil-associated products correlate with the development and severity of COPD. The peptide FMLP is an active component of CS. FMLP interacts on the neutrophil and macrophage membranes with a high-affinity receptor subtype (FPR1) and with a low-affinity subtype FPRL1, promoting a chemotactic response, superoxide anion production, and degranulation. Bacterial colonization of the lower respiratory tract and lung cell damage may represent further sources of formyl peptides in patients with COPD. We investigated the role of FPR in a mouse model on lung inflammation and emphysema induced by CS. Here, we report the novel observation that genetic ablation of the FPR1 gene (Fpr1) confers protection from smoking-induced lung emphysema in mice. Compared with wild-type mice, Fpr1 knockout mice displayed marked decreases in the lung migration of neutrophils and macrophages after CS exposure. Upon transgenic approach, the changes in cell numbers were accompanied by marked modulation of the expression of genes implicated in the inflammatory response. Administration of the FPR1 antagonist cyclosporine H to wild-type mice attenuated the acute inflammatory response evoked by CS. These findings may have clinical significance because current smokers and subjects with emphysema showed increased FPR expression in bronchoalveolar fluids and on peripheral neutrophils. Modulating the FPR1 signal should be explored as a potential new therapy.
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PMID:Genetic ablation of the fpr1 gene confers protection from smoking-induced lung emphysema in mice. 2246 30