Immunosuppression by pulmonary surfactant: mechanisms of action.

Wilsher, Margaret; Parker, D J; Haslam, P L

doi:10.1136/thx.45.1.3

Cited by 39 publications

(33 citation statements)

References 22 publications

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“…In our study using PMNs from adults, mediator-induced PMN-response was found to be maximally modulated (suppressed or enhanced) at surfactant concentrations suggested by others to be present in the bronchoalveolar lining fluid [44]. Whilst free arachidonic acid, lysophospholipids and surfactant protein (SP)-A may increase the inflammatory response [45], surfactant preparations lacking the hydrophilic apoproteins, SP-A and SP-D, as well as the phosphatidyl fraction may contribute to reduced host defence by downregulation of inflammatory processes [11,45]. However.…”

Section: Discussionmentioning

confidence: 91%

“…Under pathological conditions leading to respiratory failure, such as immaturity, haemodynamic impairment and inflammation, the close proximity of the vascular bed and alveolar space may, however, favour an undesirable bidirectional protein leak and cell exchange. Plasma proteins and blood cells inactivate surfactant [6][7][8], whilst surfactant preparations and their isolated constituents exert various effects on cell systems involved in the local and systemic immune response [9][10][11][12].…”

mentioning

confidence: 99%

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In vitro modulation of induced neutrophil activation by different surfactant preparations

Tegtmeyer¹,

Gortner²,

Ludwig³

et al. 1996

Eur Respir J

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Section: Discussionmentioning

confidence: 91%

mentioning

confidence: 99%

In vitro modulation of induced neutrophil activation by different surfactant preparations

Tegtmeyer¹,

Gortner²,

Ludwig³

et al. 1996

Eur Respir J

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“…It remains speeulative whether this was due to biologieal or technical reasons. Only little IFN-y may be produced in the alveolar spaces in vivo due to the immunosuppressive effect of surfactant [36,37] or the poor antigen-presenting function of alveolar macrophages [38] assoeiated with their release of suppressor factors [39]. Locally produced IFN-y may also be bound to receptors [40] or inactivated by an inhibitor or proteases [41].…”

Section: Discussionmentioning

confidence: 99%

In vivo levels and in vitro production of interferon-gamma in fibrosing interstitial lung diseases

C¹,

Haslam²

1992

Clinical and Experimental Immunology

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109

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SUMMARY The in vivo role of interferons in the development of fibrosis is not fully understood but it is known that interferons can suppress fibroblast proliferation and collagen synthesis in vitro. We have recently demonstrated that in a group of patients with sarcoidosis having predominant pulmonary involvement, patients with the highest levels of circulating interferon‐gamma (IFN‐y) more frequently resolved on corticosteroids, suggesting that they had a less‘fibrotic’ component to their disease. We now report that in two other diseases, where the tendency to develop pulmonary fibrosis is greater than in sarcoidosis, namely cryptogenic fibrosing alveolitis (CFA) and fibrosing alveolitis associated with the systemic connective tissue disease progressive systemic sclerosis (FA + PSS), very few patients have elevations in IFN‐γ in their serum. However, as in sarcoidosis, those with the highest levels responded to corticosteroids (P < 0·05). Attempts to measure IFN‐γ levels in the lungs, using cell‐free bronchoalveolar lavage (BAL) fluid supernatants, were negative in all the study groups, suggesting that these samples may be inadequate for such studies. To investigate whether there might be an intrinsic defect in T lymphocyte function associated with predisposition to fibrosing lung diseases, we then investigated the in vitro production of IFN‐y by lymphocytes separated from the blood of 18 untreated patients (six with CFA, six with FA + PSS and six with sarcoidosis). IFN‐γ production was impaired in 10 (56%) (two with CFA, four with FA + PSS and four with sarcoidosis). A higher proportion of the fibrosing alveolitis patients (CFA or FA + PSS) with impaired IFN‐γ production have subsequently shown spontaneous lung functional deterioration. These findings suggest that impaired IFN‐γ release might be a potentiating factor in the pathogenesis of these fibrosing lung diseases.

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“…Moreover, SP-A binds to pollen grains, suggesting a role in protection against particles [51]. Surfactant phospholipids seem to be able to downregulate local lymphocyte activities [45,52,53]. Recently, SP-A has also been shown to inhibit lymphocyte proliferation and cytokine production in vitro [54].…”

Section: Origin and Compositionmentioning

confidence: 99%

The role of pulmonary surfactant in obstructive airways disease

Hohlfeld

Fabel²,

Hamm³

1997

Eur Respir J

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Pulmonary surfactant research has an increasing impact on treatment considerations in adult respiratory disorders, above all acute respiratory distress syndrome (ARDS). Obstructive airways diseases have only been sporadically addressed in this respect. In the last decade, direct and circumstantial evidence for surfactant as a contributing factor in the regulation of airway calibre has emerged.Morphologically, a bronchiolar surfactant layer has been demonstrated, whereby the airways are mostly supplied by alveolar surfactant components via the mucociliary escalator. Functionally, prevention of airway film collapse and collapse of the airway walls are important surfactant properties in maintaining airway stability. In addition to its surface activity, airway surfactant improves bronchial clearance and regulates airway liquid balance, thus indirectly modulating airway wall thickness and airway diameter. Surfactant has furthermore been shown to modulate the function of respiratory inflammatory cells. Its immunomodulatory activity includes suppression of cytokine secretion and transcription factor activation. This may be of importance in the inflammatory network of asthma.Thus, dysfunction of surfactant in obstructive lung disease might be one of the mechanisms leading to increased airway resistance, which is commonly thought to be due to narrowing of airways under humoral and nervous control. In animal models of asthma, surfactant dysfunction was demonstrated, which was possibly due to protein inhibition. Furthermore, surfactant therapy seems to be capable of preventing allergen-induced bronchoconstriction. Human studies on surfactant impairment in obstructive airways diseases are still scarce but the data available are consistent with animal studies.Antiobstructive pharmacotherapy, mainly with corticosteroids, might influence and improve airway surfactant balance, but the exact mechanisms and the overall effect of pharmacotherapy on surfactant function in obstructive airways disease has to be further elucidated. Our knowledge about the role of pulmonary surfactant in obstructive airways disease is still limited, but there is convincing evidence that pulmonary surfactant plays a role in keeping the airways open.

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Immunosuppression by pulmonary surfactant: mechanisms of action.

Cited by 39 publications

References 22 publications

In vitro modulation of induced neutrophil activation by different surfactant preparations

In vitro modulation of induced neutrophil activation by different surfactant preparations

In vivo levels and in vitro production of interferon-gamma in fibrosing interstitial lung diseases

The role of pulmonary surfactant in obstructive airways disease

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