Surfactant strengthens the inhibitory effect of C-reactive protein on human lung macrophage cytokine release

Abstract

strengthens the inhibitory effect of C-reactive protein on human lung macrophage cytokine release. Am J Physiol Lung Cell Mol Physiol 284: L466-L472, 2003. First published November 15, 2002 10.1152/ajplung.00325.2002In this study we investigated the effect of acute-phase levels of C-reactive protein (CRP) on cytokine production by pulmonary macrophages in the presence or absence of pulmonary surfactant. Both human alveolar and interstitial macrophages as well as human surfactant were obtained from multiple organ donor lungs. Precultured macrophages were stimulated with LPS alone or together with IFN-␥ in the presence or absence of CRP, surfactant, and combinations. Releases of TNF-␣ and of IL-1␤ to the medium were determined. We found that CRP could modulate lung inflammation in humans by decreasing the production of proinflammatory cytokines by both alveolar and interstitial macrophages stimulated with LPS alone or together with IFN-␥. The potential interaction between CRP and surfactant phospholipids did not overcome the effect of either CRP or surfactant on TNF-␣ and IL-1␤ release by lung macrophages. On the contrary, CRP and pulmonary surfactant together had a greater inhibitory effect than either alone on the release of proinflammatory cytokines by lung macrophages.

Surfactant Protein A Prevents IFN-γ/IFN-γ Receptor Interaction and Attenuates Classical Activation of Human Alveolar Macrophages

“…Similarly to the observations using rat aMfs presented above, IFN-g itself was not capable of significantly stimulating TNF-a secretion. However, IFN-g increased the levels of LPS-induced TNF-a secretion by human aMfs, as previously reported (29), and this further increase was significantly impaired by SP-A. Therefore, similar to the case of rat aMfs, SP-A is capable of limiting the production of proinflammatory cytokines by human aMfs exposed to the classical activation stimuli LPS + IFN-g.…”

“…FBS, 100 U/ml penicillin, and 100 mg/ml streptomycin, supplemented with 2 mM glutamine) (Lonza). Human and rat aMfs were purified by adherence for 90 min at 37˚C under a 95% air-5% CO 2 atmosphere in 150-cm 2 culture flasks as reported previously (29,30). Adherent cells were 94.0 6 1.1% viable (trypan blue exclusion test).…”

Physical properties and surface activity of surfactant‐like membranes containing the cationic and hydrophobic peptide KL4

“…The sample solutions were prepared by mixed stock solution of the lipid and the peptide, both prepared in chloroform ⁄ methanol, to achieve the desired lipid ⁄ peptide ratio. Human lung surfactant was isolated and characterized as described previously [37].…”

Cholesterol Rules

“…On the other hand, the presence of cholesterol along with other unsaturated phospholipid species in the native material suggests the possibility of a fluid ordered/fluid disordered-like phase coexistence (distinguished in part by their cholesterol content) under physiologically relevant conditions (10). Even though lung surfactant has cholesterol concentrations of up to 20 -22 mol % (11,12), there is no clear understanding of how this molecule impacts the lateral structure of the native material. The presence of cholesterol could thus have important consequences for the lateral organization of the native pulmonary surfactant material, illustrating another example of the fundamental role of cholesterol in modulating the lateral structure of membranes, as the raft hypothesis proposes (13,14).…”