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This Article Full Text Full Text (PDF) All Versions of this Article: 288/6/L1070    most recent 00386.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Tonks, A. Articles by Jackson, S. K. Search for Related Content PubMed PubMed Citation Articles by Tonks, A. Articles by Jackson, S. K.

Surfactant phospholipid DPPC downregulates monocyte respiratory burst via modulation of PKC

Departments of ¹Haematology and ²Medical Microbiology, School of Medicine, Wales College of Medicine, Cardiff University; and ³School of Applied Sciences, University of Wales Institute, Cardiff, United Kingdom

Submitted 13 October 2004 ; accepted in final form 21 January 2005

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 PKC isoform but not PKC. 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 PKC isoform.

superoxide; signal transduction; dipalmitoyl phosphatidylcholine; inflammation; reactive oxygen intermediate