Surfactant phospholipid DPPC downregulates monocyte respiratory burst via modulation of PKC

Abstract

Pulmonary surfactant phospholipids have been shown previously to regulate inflammatory functions of human monocytes. This study was undertaken to delineate the mechanisms by which pulmonary surfactant modulates the respiratory burst in a human monocytic cell line, MonoMac-6 (MM6). Preincubation of MM6 cells with the surfactant preparations Survanta, Curosurf, or Exosurf Neonatal inhibited the oxidative response to either lipopolysaccharide (LPS) and zymosan or phorbol 12-myristate 13-acetate (PMA) by up to 50% ( P < 0.01). Preincubation of MM6 cells and human peripheral blood monocytes with dipalmitoyl phosphatidylcholine (DPPC), the major phospholipid component of surfactant, inhibited the oxidative response to zymosan. DPPC did not directly affect the activity of the NADPH oxidase in a MM6 reconstituted cell system, suggesting that DPPC does not affect the assembly of the individual components of this enzyme into a functional unit. The effects of DPPC were evaluated on both LPS/zymosan and PMA activation of protein kinase C (PKC), a ubiquitous intracellular kinase, in MM6 cells. We found that DPPC significantly inhibited the activity of PKC in stimulated cells by 70% ( P < 0.01). Western blotting experiments demonstrated that DPPC was able to attenuate the activation of the PKCδ isoform but not PKCα. These results suggest that DPPC, the major component of pulmonary surfactant, plays a role in modulating leukocyte inflammatory responses in the lung via downregulation of PKC, a mechanism that may involve the PKCδ isoform.

Surfactant lipids regulate LPS-induced interleukin-8 production in A549 lung epithelial cells by inhibiting translocation of TLR4 into lipid raft domains

“…Moreover, in this study, the artifi cial surfactant preparations used are devoid of the hydrophilic proteins SP-A and SP-D and contain reduced amounts of the hydrophobic proteins SP-B and SP-C ( 39 ). Furthermore, we show that equivalent antiinfl ammatory activity was produced by the major surfactant phospholipid species, DPPC, at concentrations that have been measured for this lipid in natural surfactant ( 44,45 ). Previous studies, from our laboratories and others, have shown that DPPC has an immunoregulatory role on leukocytes ( 31-36, 40, 46 ).…”

Non-Invasive Ventilation and Surfactant Therapy

“…Furthermore, plasmalogens, which are antioxidant phospholipids, are also present in higher amounts in PA. Higher plasmalogen content in the tracheal aspirate in preterm infants is associated with a lower risk for developing BPD [75]. Higher amounts of DPPC also offers better anti-inflammatory properties [76], and down-regulates the respiratory burst via modulation of protein kinase C [77]. PA has been approved for use with an initial dose of 200 mg/kg, and 100 mg/kg for subsequent doses, whereas, BE is used at 100 mg/kg, and CA at 105 mg/kg for first and subsequent doses.…”

Ras-induced reactive oxygen species promote growth factor–independent proliferation in human CD34+ hematopoietic progenitor cells

“…Some experiments were carried out in the presence of either 5 g/mL superoxide dismutase (SOD), 100 g/mL catalase, 50M diphenyleneiodonium (DPI), 1mM apocynin, or 5M rotenone (Sigma). Human peripheral blood monocytes stimulated with opsonised zymosan 23 were used for comparative purposes.…”