Enhancement of biophysical activity of lung surfactant extracts and phospholipid-apoprotein mixtures by surfactant protein A

Venkitaraman, A.R.; Hall, Stephen B.; Whitsett, Jeffrey A.; Notter, Robert H.

doi:10.1016/0009-3084(90)90101-v

Cited by 88 publications

(66 citation statements)

References 7 publications

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“…The role of SP-A in maintaining low alveolar surface tensions in vivo remains unclear. Although available lung injury studies in SP-A Ϫ/Ϫ mice do not yet support a primary physiologic role for SP-A in surfactant biophysical function, multiple reports of SP-A protective effects on surfactant surface tension in in vitro studies (42,43) and in other SP-A animal models (45) warrant additional investigation in SP-A Ϫ/Ϫ models under a variety of experimental conditions.…”

Section: Effect Of N-terminal Interchange On the Association Of Sp-a mentioning

confidence: 99%

The Role of Pulmonary Collectin N-terminal Domains in Surfactant Structure, Function, and Homeostasis in Vivo

Palaniyar¹,

Zhang²,

Kuzmenko³

et al. 2002

Journal of Biological Chemistry

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Lung surfactant is a mixture of phospholipids, neutral lipids, and surfactant protein A (SP-A) 1 SP-B, SP-C, and SP-D, which are secreted into the air spaces by alveolar type II cells and Clara cells of the distal pulmonary epithelium (1). Although the primary function of surfactant is to reduce surface tension, the contribution of each molecular component to surface activity is not completely understood. Surfactant phospholipids form a film at the air-liquid interface that maintains air space patency by resisting compression as the alveolar radius decreases during expiration. Data from in vitro experiments, gene-targeted animals, and naturally occurring mutations in humans indicate that the hydrophobic surfactant proteins, SP-B and SP-C, participate in the assembly and biophysical properties of the surfactant film (2). The hydrophilic surfactant proteins, SP-A and SP-D, have a complex functional profile. The recognition that SP-A and SP-D are structurally homologous to mannosebinding protein has identified them as members of the collectin family of innate opsonins and directed attention to their host defense properties (3). Like mannose-binding protein, SP-A and SP-D bind to a wide range of microorganisms and enhance microbial phagocytosis and killing by alveolar macrophages. These in vitro activities appear to be physiologically relevant, since gene-targeted SP-A Ϫ/Ϫ and SP-D Ϫ/Ϫ mice clear microbial infections less effectively than pulmonary collectin-sufficient mice (4 -7). However, SP-A Ϫ/Ϫ and SP-D Ϫ/Ϫ mice also exhibit abnormalities of surfactant structure, metabolism and function (8 -10). Surfactant isolated from SP-A Ϫ/Ϫ mice does not contain the large aggregate tubular myelin and has impaired surface activity in the presence of plasma inhibitors (11). SP-D Ϫ/Ϫ mice develop progressive alveolar phospholipidosis and air space dilation (9, 10), associated with increased macrophage production of metalloproteinases and oxidant species (12). All of these defects are corrected by lung-specific expression of the cognate collectin in the SP-A Ϫ/Ϫ and SP-D Ϫ/Ϫ mice (13, 14). The structural basis of SP-A and SP-D surfactant functions has been explored by mutagenesis using in vitro and in vivo analyses. The primary structure of both proteins includes an N-terminal segment containing interchain linkages formed by Cys residues, a collagen-like region of Gly-X-Y repeats, a hydrophobic "neck" domain, and a carbohydrate recognition domain (CRD) (15,16). Trimeric association of subunits occurs by the folding of the collagen-like domains into triple helices (17) and coiled-coil bundling of ␣-helices in the neck (18). In the fully assembled molecules, the N-terminal sequences and di- ϩ/ϩ mice disrupted oligomeric assembly of the endogenous SP-D and produced air space dilation and foamy macrophage formation without phospholipidosis (24). These data suggested that the in vivo activity of SP-D is dependent on its oligomeric structure. The purpose of this study was to examine the role of the N-terminal segment-dependent olig...

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Section: Effect Of N-terminal Interchange On the Association Of Sp-a mentioning

confidence: 99%

The Role of Pulmonary Collectin N-terminal Domains in Surfactant Structure, Function, and Homeostasis in Vivo

Palaniyar¹,

Zhang²,

Kuzmenko³

et al. 2002

Journal of Biological Chemistry

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“…It regulates surfactant phospholipid metabolism, facilitating recycling of endogenous surfactant between the type II cells and the alveolar compartment [3,4], and regulates transformation of lamellar bodies to tubular myelin [5]. Several investigators have reported that the presence of SP-A makes surfactant more resistant to inactivation by blood proteins in vitro [6,7] as well as in ventilated newborn experimental animals [8]. YAMADA et al [9] found that addition of SP-A to modified bovine surfactant (Survanta®, Abbott, North Chicago, IL, USA) potentiated the therapeutic effect of the surfactant on dynamic and static lung compliance in ventilated premature newborn rabbits.…”

mentioning

confidence: 99%

Biophysical and physiological properties of a modified porcine surfactant enriched with surfactant protein A

Sun¹,

Curstedt²,

Lindgren³

et al. 1997

Eur Respir J

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Surfactant protein A (SP-A), a major protein component of natural pulmonary surfactant, is absent in exogenous surfactants currently used in clinical practice.We investigated the physical and physiological properties of one of these modified natural surfactants (Curosurf®) after enrichment with 5% SP-A (SP-A-Curosurf). A pulsating bubble system was used for in vitro assessments and ventilated newborn rabbits for evaluation of in vivo effects.In the presence of various potential inhibitors (meconium 5 mg·mL -1 , fibrinogen 5 mg·mL -1 , albumin 25 mg·mL -1 , or whole serum proteins 25 mg·mL -1 ), Curosurf at a concentration of 5 mg·mL -1 was inactivated while SP-A-Curosurf and natural porcine surfactant at the same concentration had normal maximum and minimum surface tension. This protective effect of SP-A was calcium dependent. In immature newborn rabbits, the improvement of lung-thorax compliance observed after treatment with 100 mg·kg -1 of SP-A-Curosurf was equivalent to that obtained with 200 mg·kg -1 of Curosurf. Similarly, in near-term newborn rabbits with respiratory failure induced by instillation of fibrinogen via the airways, the increase in compliance after administration of 100 mg·kg -1 of SP-A-Curosurf corresponded to that seen after treatment with 200 mg·kg -1 of Curosurf, whereas Curosurf at a dose of 100 mg·kg -1 had no substantial effect.Our data thus indicate that surfactant protein A increases the resistance of Curosurf to inactivation under in vivo conditions.

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“…SP-A appears to be particularly effective in protecting surfactants containing SP-B and SP-C from inhibition by plasma proteins in vitro (17,18). Using a premature rabbit model of surfactant deficiency we examined the effect of increasing amounts of human plasma on a complete natural dog surfactant (containing SP-A, SP-B, and SP-C), on a dog lung surfactant extract (containing only SP-B and SP-C), and on a surfactant extract supplemented with SP-A.…”

mentioning

confidence: 99%

Surfactant Apoprotein A Modifies the Inhibitory Effect of Plasma Proteins on Surfactant Activity In Vivo

et al. 1995

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Enhancement of biophysical activity of lung surfactant extracts and phospholipid-apoprotein mixtures by surfactant protein A

Cited by 88 publications

References 7 publications

The Role of Pulmonary Collectin N-terminal Domains in Surfactant Structure, Function, and Homeostasis in Vivo

The Role of Pulmonary Collectin N-terminal Domains in Surfactant Structure, Function, and Homeostasis in Vivo

Biophysical and physiological properties of a modified porcine surfactant enriched with surfactant protein A

Surfactant Apoprotein A Modifies the Inhibitory Effect of Plasma Proteins on Surfactant Activity In Vivo

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