scholarly journals The protective effect of CXC chemokine receptor 2 antagonist on experimental bronchopulmonary dysplasia induced by postnatal systemic inflammation

2021 ◽  
Vol 64 (1) ◽  
pp. 37-43
Author(s):  
Seung Hyun Lee ◽  
Chang Won Choi
Keyword(s):  
Surface Area ◽  
Bronchopulmonary Dysplasia ◽  
Systemic Inflammation ◽  
Chemokine Receptor ◽  
Sprague Dawley ◽  
Alveolar Surface Area ◽  
Cxc Chemokine ◽  
Cxcr2 Antagonist ◽  
Alveolar Surface ◽  
Cord Length

Background: Animal studies have shown that a leukocyte influx precedes the development of bronchopulmonary dysplasia (BPD) in premature sheep. The CXC chemokine receptor 2 (CXCR2) pathway has been implicated in the pathogenesis of BPD because of the predominance of CXCR2 ligands in tracheal aspirates of preterm infants who later developed BPD.Purpose: To test the effect of CXCR2 antagonist on postnatal systemic and pulmonary inflammation and alveolarization in a newborn Sprague-Dawley rat model of BPD.Methods: Lipopolysaccharide (LPS) was injected intraperitoneally (i.p.) into the newborn rats on postnatal day 1 (P1), P3, and P5 to induce systemic inflammation and inhibit alveolarization. In the same time with LPS administration, CXCR2 antagonist (SB-265610) or vehicle was injected i.p. to investigate whether CXCR2 antagonist can alleviate the detrimental effect of LPS on alveolarization by attenuating inflammation. On P7 and P14, bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) were collected from the pups. To assess alveolarization, mean cord length and alveolar surface area were measured on 4 random nonoverlapping fields per animal in 2 distal lung sections at ×100 magnification.Results: Early postnatal LPS administration significantly increased neutrophil counts in BALF and PB and inhibited alveolarization, which was indicated by a greater mean cord length and lesser alveolar surface area. CXCR2 antagonist significantly attenuated the increase of neutrophil counts in BALF and PB and restored alveolarization as indicated by a decreased mean cord length and increased alveolar surface area in rat pups exposed to early postnatal systemic LPS.Conclusion: CXCR2 antagonist preserved alveolarization by alleviating pulmonary and systemic inflammation induced by early postnatal systemic LPS administration. These results suggest that CXCR2 antagonist can be considered a potential therapeutic agent for BPD that results from disrupted alveolarization induced by inflammation.

Pulmonary epithelial liquid absorption, expressed in relation to alveolar surface area, is reduced in fetal lambs following in utero tracheal occlusion

2002 ◽  
Vol 34 (4) ◽  
pp. 278-286 ◽  
Author(s):  
M.G. Davey ◽  
H.L. Hedrick ◽  
J.M. Mendoza ◽  
M. Kanai ◽  
N.S. Adzick ◽  
...  
Keyword(s):  
Surface Area ◽  
In Utero ◽  
Tracheal Occlusion ◽  
Alveolar Surface Area ◽  
Liquid Absorption ◽  
Alveolar Surface

scholarly journals Effects of leptin deficiency on postnatal lung development in mice

2008 ◽  
Vol 105 (1) ◽  
pp. 249-259 ◽  
Author(s):  
Kewu Huang ◽  
Richard Rabold ◽  
Eric Abston ◽  
Brian Schofield ◽  
Vikas Misra ◽  
...  
Keyword(s):  
Surface Area ◽  
Morphometric Analysis ◽  
Lung Development ◽  
Age Groups ◽  
Lung Parenchyma ◽  
Lung Maturation ◽  
Alveolar Surface Area ◽  
Leptin Deficiency ◽  
Postnatal Lung Development ◽  
Alveolar Surface

Leptin modulates energy metabolism and lung development. We hypothesize that the effects of leptin on postnatal lung development are volume dependent from 2 to 10 wk of age and are independent of hypometabolism associated with leptin deficiency. To test the hypotheses, effects of leptin deficiency on lung maturation were characterized in age groups of C57BL/6J mice with varying Lep ob genotypes. Quasi-static pressure-volume curves and respiratory impedance measurements were performed to profile differences in respiratory system mechanics. Morphometric analysis was conducted to estimate alveolar size and number. Oxygen consumption was measured to assess metabolic rate. Lung volume at 40-cmH2O airway pressure (V40) increased with age in each genotypic group, and V40 was significantly ( P < 0.05) lower in leptin-deficient ( ob/ ob) mice beginning at 2 wk. Differences were amplified through 7 wk of age relative to wild-type (+/+) mice. Morphometric analysis showed that alveolar surface area was lower in ob/ ob compared with +/+ and heterozygote ( ob/+) mice beginning at 2 wk. Unlike the other genotypic groups, alveolar size did not increase with age in ob/ ob mice. In another experiment, ob/ ob at 4 wk received leptin replacement (5 μg·g−1·day−1) for 8 days, and expression levels of the Col1a1, Col3a1, Col6a3, Mmp2, Tieg1, and Stat1 genes were significantly increased concomitantly with elevated V40. Leptin-induced increases in V40 corresponded with enlarged alveolar size and surface area. Gene expression suggested a remodeling event of lung parenchyma after exogenous leptin replacement. These data support the hypothesis that leptin is critical to postnatal lung remodeling, particularly related to increased V40 and enlarged alveolar surface area.

Cancer cachexia alters intracellular surfactant metabolism but not total alveolar surface area

2012 ◽  
Vol 138 (5) ◽  
pp. 803-813 ◽  
Author(s):  
Tilman Graulich ◽  
Suman Kumar Das ◽  
Gabriela Krasteva ◽  
Clemens Ruppert ◽  
Lars Wessels ◽  
...  
Keyword(s):  
Surface Area ◽  
Cancer Cachexia ◽  
Alveolar Surface Area ◽  
Alveolar Surface ◽  
Surfactant Metabolism

Estrogen receptor regulation of pulmonary alveolar dimensions: alveolar sexual dimorphism in mice

2006 ◽  
Vol 290 (5) ◽  
pp. L866-L870 ◽  
Author(s):  
Donald Massaro ◽  
Gloria DeCarlo Massaro
Keyword(s):  
Estrogen Receptor ◽  
Sexual Dimorphism ◽  
Surface Area ◽  
Body Mass ◽  
Female Rats ◽  
Female Mice ◽  
Alveolar Surface Area ◽  
Rats And Mice ◽  
Alveolar Surface ◽  
Respective Species

Female rats and mice have smaller and, per body mass (BM), more alveoli and alveolar surface area (Sa) than males of their respective species. This sexual dimorphism becomes apparent about the time of sexual maturity. It is prevented in rats (not tested in mice) by ovariectomy at age 3 wk. In female mice, estrogen receptor (ER)-α and ER-β are required for formation of alveoli of appropriate size and number. We now report the average volume of an alveolus (v̄a) and the number of alveoli per body mass (Na/BM) were not statistically different between ER-α−/− and wild type (wt) males. However, the combination of a larger value for v̄a and a smaller value for Na/BM, though neither parameter achieved a statistically significant intergroup difference, resulted in a statistically significant lower Sa/BM in ER-α−/− males compared with wt males. In ER-β−/− males, v̄a was bigger and Na/BM and Sa/BM were lower compared with wt males. Wt males had larger alveoli and lower Na/BM and Sa/BM than wt females. The wt sexual dimorphism of v̄a, Na/BM, and Sa/BM was absent in ER-α−/− mice. Alveolar size did not differ between ER-β−/− females and males but Na/BM and Sa/BM were greater in ER-β−/− females than in ER-β−/− males. The results in male mice, with prior findings in female mice, 1) demonstrate estrogen receptors have a smaller effect on alveolar dimensions in male than female mice, 2) show ER-α and ER-β are required for the sexual dimorphism of alveolar size, and 3) show ER-α is needed for the sexual dimorphism of body mass-specific alveolar number and surface area.

Effect of change in particle number on pulmonary clearance of aerosolized 99mTc-DTPA

1989 ◽  
Vol 66 (6) ◽  
pp. 2750-2755 ◽  
Author(s):  
S. Groth ◽  
J. Mortensen ◽  
P. Lange ◽  
S. Vest ◽  
N. Rossing ◽  
...  
Keyword(s):  
Surface Area ◽  
Absorption Rate ◽  
Particle Number ◽  
The Other ◽  
Inhaled Particles ◽  
Diffusion Limited ◽  
Alveolar Surface Area ◽  
Pulmonary Clearance ◽  
Jet Nebulizers ◽  
Alveolar Surface

Pulmonary clearance (PCl) of inhaled aerosolized 99mTc-diethylenetriamine pentaacetic acid (DTPA) across the alveolocapillary membrane is diffusion limited. Therefore, if the mixing of the 99mTc-DTPA in the aqueous hypophase underlying surfactant is slow or incomplete or if there were no hypophase, an increase in the alveolar surface area occupied by 99mTc-DTPA particles would increase the absorption rate. The aim of this study was to examine whether there is an effect on PCl of changing the number of inhaled particles. The change in particle number was accomplished by a setup of four parallel jet nebulizers feeding a central delivery chamber of 400 cm3. We performed two kinds of experiments in eight healthy nonsmokers between 28 and 52 yr of age. In the first experiment, 99mTc-DTPA in saline was nebulized in one nebulizer, while saline was nebulized in the other three. In the second experiment the number of inhaled particles containing 99mTc-DTPA was increased by a factor of four by nebulizing 99mTc-DTPA in saline in all four nebulizers simultaneously. Increasing the number of inhaled 99mTc-DTPA particles caused an increase in PCl of 24.2% (P less than 0.01). We conclude that there is a slight but significant effect of changing the number of DTPA particles on PCl and that this is probably due to an uneven mixing of the 99mTc-DTPA in the aqueous hypophase underlying the surfactant lining and the alveoli.

Estimating alveolar surface area during life

1992 ◽  
Vol 88 (1-2) ◽  
pp. 163-170 ◽  
Author(s):  
H.J.H. Colebatch ◽  
C.K.Y. Ng
Keyword(s):  
Surface Area ◽  
Alveolar Surface Area ◽  
Alveolar Surface

Determination of alveolar surface area and tension from in situ pressure-volume data

1970 ◽  
Vol 10 (2) ◽  
pp. 159-171 ◽  
Author(s):  
Martin J. Fisher ◽  
Michael F. Wilson ◽  
Kenneth C. Weber
Keyword(s):  
Surface Area ◽  
Volume Data ◽  
Alveolar Surface Area ◽  
Alveolar Surface

Quantitative lung morphology in Japanese waltzing mice

1978 ◽  
Vol 44 (3) ◽  
pp. 446-449 ◽  
Author(s):  
D. Bartlett ◽  
J. G. Areson
Keyword(s):  
Body Weight ◽  
Surface Area ◽  
Lung Volume ◽  
Lung Growth ◽  
Lung Morphology ◽  
Alveolar Surface Area ◽  
Albino Mice ◽  
Alveolar Surface

We have reinvestigated the question of whether exercise stimulates lung growth by determining body weight (BW), lung volume (LV), alveolar surface area (SA), and alveolar number (N) in Japanese waltzing mice, in their phenotypically normal littermates, and in normal albino mice. BW, LV, SA, and N were all less in waltzing mice than in their littermates; LV/BW, SA/BW, and N/BW were indistinguishable in the two groups. Age-matched albino mice had larger BW and smaller N/BW than the waltzers or their littermates. The results indicate that both waltzing mice and their nonwaltzing littermates have more highly compartmentalized lungs than albino mice of the same age. However, the data provide no support for the hypothesis that sustained exercise enhances lung growth.

Functional assessment of pulmonary capillary surface area in the 2-mo-old lamb

1991 ◽  
Vol 70 (4) ◽  
pp. 1677-1685 ◽  
Author(s):  
B. R. Pitt ◽  
G. Lister ◽  
J. J. Perez Fontan ◽  
P. Davies
Keyword(s):  
Surface Area ◽  
Pulmonary Toxicity ◽  
Antineoplastic Agent ◽  
Maximal Velocity ◽  
Alveolar Surface Area ◽  
Pulmonary Capillary ◽  
Significant Difference ◽  
Normal Variability ◽  
Alveolar Surface

We recently reported that measurements of the maximal velocity of pulmonary endothelial angiotensin-converting enzyme (Vmax) in vivo provide information regarding microvascular surface area in the developing lamb. To obviate any subtle influences of development on Vmax aside from simple increases in surface area, we correlated Vmax with postmortem stereological assessments of alveolar surface area in the relatively mature lung of the 2-mo-old lamb (n = 14). We attempted to increase the range of surface area beyond its normal variability by injecting nine of the lambs with bleomycin, an antineoplastic agent with significant pulmonary toxicity in other species. Vmax, measured shortly after birth and then weekly, increased monotonically in all lambs. Despite their wide dispersion, Vmax and the stereological determinations correlated strongly at 2 mo of age, confirming that Vmax is a robust indicator of the surface area of the air-blood barrier. There was no significant difference in either measurement between the control lambs and those treated with bleomycin, suggesting that the newborn lamb is resistant to the effect of this agent.

scholarly journals Retinoic acid in alveolar development, maintenance and regeneration

2004 ◽  
Vol 359 (1445) ◽  
pp. 799-808 ◽  
Author(s):  
Malcolm Maden ◽  
Matthew Hind
Keyword(s):  
Retinoic Acid ◽  
Surface Area ◽  
Biologically Active ◽  
Remarkable Effect ◽  
Alveolar Surface Area ◽  
Alveolar Development ◽  
Retinoid Binding Proteins ◽  
Dose Dependent ◽  
Experimental Emphysema ◽  
Alveolar Surface

Recent data suggest that exogenous retinoic acid (RA), the biologically active derivative of vitamin A, can induce alveolar regeneration in a rat model of experimental emphysema. Here, we describe a mouse model of disrupted alveolar development using dexamethasone administered postnatally. We show that the effects of dexamethasone are concentration dependent, dose dependent, long lasting and result in a severe loss of alveolar surface area. When RA is administered to these animals as adults, lung architecture and the surface area per unit of body weight are completely restored to normal. This remarkable effect may be because RA is required during normal alveolar development and administering RA re–awakens gene cascades used during development. We provide evidence that RA is required during alveologenesis in the mouse by showing that the levels of the retinoid binding proteins, the RA receptors and two RA synthesizing enzymes peak postnatally. Furthermore, an inhibitor of RA synthesis, disulphiram, disrupts alveologenesis. We also show that RA is required throughout life for the maintenance of lung alveoli because when rats are deprived of dietary retinol they lose alveoli and show the features of emphysema. Alveolar regeneration with RA may therefore be an important novel therapeutic approach to the treatment of respiratory diseases characterized by a reduced gas–exchanging surface area such as bronchopulmonary dysplasia and emphysema for which there are currently no treatments.

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