Maturation of the Rabbit Alveolar Macrophage during Animal Development. I. Perinatal Influx into Alveoli and Ultrastructural Differentiation

Zeligs, Barbara J.; Nerurkar, Lata S.; Bellanti, Joseph A.; Zeligs, Joseph D.

doi:10.1203/00006450-197703000-00011

Cited by 79 publications

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“…Our laboratory has previously found that spontaneous MMP-9 secretion by alveolar macrophages in newborn rats significantly varied with the lung growth phase (10). The number of alveolar macrophages is expected to be very low in premature neonates (10,38), as confirmed here, and this may also contribute to the lower MMP-9 levels observed with increasing prematurity. Hyaline membrane disease was associated with increased MMP-9 level in the airways on days 3 and 5 of life; this level correlated with the number of inflammatory cells, suggesting that MMP-9 mainly originated from recruited, activated alveolar macrophages and neutrophils.…”

Section: Discussionsupporting

confidence: 54%

Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia

Danan

Jarreau

Franco

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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2002.-Matrix-degrading metalloproteinases may play a role in the pathophysiology of bronchopulmonary dysplasia (BDP). We, therefore, evaluated correlations between gelatinase activities [metalloproteinase (MMP)-2 and MMP-9] or tissue inhibitor of metalloproteinase (TIMP)-1 levels present in the airways during the initial phase of hyaline membrane disease and the onset of BPD. Tracheal aspirates were obtained within 6 h of birth (day 0) from 64 intubated neonates with a gestational age Յ30 wk. Forty-five neonates were resampled on day 3 or 5. Total MMP-2 level measured by zymography fell with time, whereas total MMP-9 level and TIMP-1 levels, assayed by ELISA, increased; the MMP-9 increase correlated with the increase in airway inflammatory cell numbers. Among the parameters measured on day 0, 3, or 5, lower total MMP-2 level, lower birth weight, and higher fraction of inspired oxygen on day 0 were significantly and independently associated with the development of BPD. In conclusion, MMP-9 level and TIMP-1 levels increased after birth but are not linked to BPD outcome. In contrast, low MMP-2 level at birth is strongly associated with the development of BPD. metalloproteinase; lung development; newborn; extracellular matrix PREMATURE NEONATES WITH HYALINE membrane disease are at risk of developing bronchopulmonary dysplasia (BPD), as a sequel of both the disease and its treatment. The pathogenesis is unclear, but BPD is thought to result from damage to an immature lung. Mechanical ventilation, oxygen therapy, and airway inflammatory responses have all been implicated in the development of BPD (19). These insults appear to interfere with normal lung maturation, which is incomplete at birth. In particular, they appear to alter alveolar formation, on the basis of morphometric studies of severe BPD (3, 24). Alveolar formation is characterized by the multiplication of alveolar septa and the thinning of interalveolar walls, both of which require intense remodeling of the pulmonary extracellular matrix (4). Changes in matrix turnover have been experimentally linked to abnormal alveolar formation (20). The proteinase-antiproteinase balance in the lung is a key factor in harmonious matrix turnover. In particular, matrix metalloproteinases (MMPs), which can synergistically digest the major macromolecules of connective tissue matrices, have been implicated in physiological regulation of lung growth. The MMP gelatinase A (MMP-2) has been shown to play a role in the major collagen turnover that occurs during early postnatal rat lung growth (1, 2). We postulated that MMP-2 might also participate in human lung development and that inadequate MMP-2 levels in premature lungs exposed to insults could contribute to impaired lung growth and thus to BPD. We also postulated that MMPs may be secreted in excess during the inflammatory response associated with hyaline membrane disease and may, therefore, lead to tissue degradation. Gelatinase B (MMP-9) is the main MMP released by inflammatory cells such as neutrophils and alveolar macroph...

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Section: Discussionsupporting

confidence: 54%

Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia

Danan

Jarreau

Franco

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In contrast, in rabbits AM are present in BAL samples taken prior to birth and remain the predominate cell type found in lung washings throughout postnatal development (24,25). The cell populations present in pulmonary air spaces of newborn infants are not well defined.…”

Section: Discussionmentioning

confidence: 90%

“…The early postnatal development of AM function has been studied extensively in rabbits (24,25,(28)(29)(30)(31). Using an in vitro assay Sieger (25) found that AM from newborn rabbits were able to kill opsonized bacteria as efficiently as adult AM.…”

Section: Discussionmentioning

confidence: 99%

“…One possibility is that the biochemical mechanisms required for intracellular killing may not be fully developed at birth (28). A second possibility is that this function may be inhibited by the large quantities of phagocytosed surfactant material present in AM during early postnatal life (24). Sherman et al (31) exposed rabbits to aerosols of S. aureus and measured phagocytosis and bactericidal activities in situ.…”

Section: Discussionmentioning

confidence: 99%

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Postnatal Maturation of Pulmonary Antimicrobial Defense Mechanisms in Conventional and Germ- Free Lambs

1986

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ABSTRACT. The phagocytic and bactericidal capacities of ovine bronchoalveolar lavage (BAL) cells were investigated as a function of postnatal age. In addition, age-related changes in the elaboration by alveolar macrophages of chemotaxins for neutrophils, concentrations of BAL fluid and serum immunoglobulins, and serum opsonic capacity were determined. BAL cells exhibited major changes in morphology, composition, and in vitro proliferation during the 1st postnatal wk. Studies in germ-free lambs indicated that the antigenic burden of the ambient environment markedly influenced the concentration of BAL neutrophils but had no effect on the influx, phagocytic, and proliferative activities of alveolar macrophages. Phagocytic and bactericidal functions of BAL cells improved rapidly during the 1st postnatal wk, then declined, and did not reattain adult levels until day 180. The capacity of alveolar macrophages to elaborate chemotaxins for neutrophils was deficient at day 8, but not at subsequent ages. The concentration of BAL IgG, increased until day 8, fell at day 21, and then continued to increase gradually. IgA was not detected in BAL until day 21 and increased rapidly thereafter. Serum opsonic capacity at days 1 and 4 was comparable to that of adult serum, but sera from days 8 to 42 showed a marked reduction in opsonic capacity. Pulmonary antimicrobial defenses in neonatal sheep were thus found to be deficient to some degree throughout the first 3 months of life. It was not until day 180 that the parameters investigated in this study approximated those of adult sheep.

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“…Mechanical ventilation with intermittent positive airway pressure and high 0, levels might also interfere with the pulmonary defense system and cause a more rapid proliferation of bacteria (43). Nearterm rabbit fetuses born by cesarean section show a decreased capacity to kill invading microorganisms in comparison to animals that are born spontaneously, probably reflecting a delayed influx of phagocytes into the bronchoalveolar space (44). These circumstances might to some extent explain why we, in contrast to other investigators (42), could observe proliferation of GBS in near-term rabbits.…”

Section: Herting Etalmentioning

confidence: 99%

Experimental Neonatal Group B Streptococcal Pneumonia: Effect of a Modified Porcine Surfactant on Bacterial Proliferation in Ventilated Near-Term Rabbits

et al. 1994

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jWe studied bacterial proliferation in relation to surfac-bacterial numbers in both groups ventilated for 5 h, but tant treatment in a model of neonatal group B streptococcal values for surfactant-treated animals (8.96 + 0.38) were (GBS) pneumonia. Surfactant (Curosurf) was isolated from lower than those for animals receiving saline (9.46 + 0.50; pig lungs with a method preserving only polar lipids and p < 0.05). After 5 h, 96% of GBS-infected animals had hydrophobic proteins. Near-term rabbit fetuses were ven-positive blood cultures. Light microscopic examination of tilated in a body plethysmograph system. At 15 min, a the right lung of GBS-infected animals revealed inflammasuspension of GBS strain 090 Ia LD (5 mL/kg, concentra-tory changes that tended to be less prominent in surfactanttion -109/mL) was instilled intratracheally. At 30 min, treated rabbits. We conclude that intratracheal inoculation surfactant (n = 12) or sterile saline (n = 13) was adminis-of near-term rabbits with GBS resulted in a significant tered via the airways (2.5 mL/kg). A control group (n = 12) bacterial proliferation during 5 h of ventilation and that received the same volumes of saline. After 5 h the animals bacterial growth was mitigated by treatment with surfacwere killed, and samples for blood cultures and blood gases tant. (Pediatr Res 36: [784][785][786][787][788][789][790][791] 1994) were taken from the heart. The left lung was aseptically removed, weighed, homogenized, serially diluted, and cultured on blood agar plates. The results were expressed as Abbreviations mean log,, colony forming units/g lung + SD. Compared CFU, colony forming unit with animals (n = 12) killed immediately after GBS instil-GBS, group B streptococcus lation (8.13 2 0.54), there was a significant increase in RDS, respiratory distress syndrome GBS is a frequently encountered pathogen in the neonatal period (1). Vaginal colonization with GBS is commonly found in pregnant women. Vertical transmission occurs in approximately 40% of deliveries, but only approximately 1% of neonates born to these mothers develop clinical signs of GBS infection (2). If diagnosis and treatment are delayed, the condition has a substantial mortality, especially in premature infants (2). Susceptibility to GBS infections depends on host defense factors (e-g. lack of type-specific opsonizing antibodies) and Received January 26, 1994; accepted June 21, 1994. virulence factors (e-g. polysaccharide capsule) of the infecting microorganism (3-6).Animal models using rabbits, mice, and rats have been used for studies of experimental neonatal GBS infections (7)(8)(9). In these studies, the animals were either infected b y injection (7, 9) o r a bacterial suspension was nebulized via the airways in spontaneously breathing animals (8,9). Our intention was t o develop a model of GBS pneumonia in ventilated newborn rabbits infected b y intratracheal injection of a bacterial suspension.RDS and GBS pneumonia are difficult to differentiate o n clinical grounds (lo), and therefore neonates with ...

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Maturation of the Rabbit Alveolar Macrophage during Animal Development. I. Perinatal Influx into Alveoli and Ultrastructural Differentiation

Abstract: hlultiple c r p t a l cru\s-scctlon;il cclioc;trtlic~graphy ill the tli;ignosis o f cy-:111olic corigcrlit:~I l~c ;~r t disca\e. C'ircc~I;it~,~i~. 50: 230 (1074).

Cited by 79 publications

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Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia

Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia

Postnatal Maturation of Pulmonary Antimicrobial Defense Mechanisms in Conventional and Germ- Free Lambs

Experimental Neonatal Group B Streptococcal Pneumonia: Effect of a Modified Porcine Surfactant on Bacterial Proliferation in Ventilated Near-Term Rabbits

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