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Published on: June 8, 2012
Spontaneous expression of the c-sis gene and release of a platelet-derived growth factorlike molecule by human
Abstract:
Alveolar macrophages from normal individuals and patients with interstitial lung diseases spontaneously expressed a 4.2-kilobase mRNA complementary to the c-sis gene, a proto-oncogene coding for one of the chains of platelet-derived growth factor (PDGF). Concomitantly, these cells released a mediator with the properties of PDGF, including: chemotactic factor for smooth muscle cells whose activity was resistant to heat and acid, but sensitive to reduction; mitogenic (competence) activity for fibroblasts; ability to compete with PDGF for its receptor; and precipitated by an anti-PDGF antibody. While blood monocytes did not contain c-sis mRNA transcripts, monocytes matured in vitro expressed c-sis, consistent with the concept that expression of c-sis occurs during the differentiation of monocytes into alveolar macrophages. Together with the known actions of PDGF, these observations suggest that the c-sis proto-oncogene and its PDGF product are part of the armamentarium available to the alveolar macrophages for normal lung defense and participation in lung inflammation.
Insights
Alveolar macrophages express the c-sis gene, producing platelet-derived growth factor (PDGF). This suggests PDGF plays a role in lung defense and inflammation, particularly during monocyte differentiation into macrophages.
Area of Science:
- Cell Biology
- Immunology
- Molecular Biology
Background:
- Alveolar macrophages are key immune cells in the lungs.
- Proto-oncogenes like c-sis are involved in cell growth and differentiation.
- Platelet-derived growth factor (PDGF) has known roles in cell signaling.
Purpose of the Study:
- To investigate the expression of the c-sis gene in alveolar macrophages.
- To determine if alveolar macrophages produce PDGF.
- To explore the role of c-sis and PDGF in lung defense and inflammation.
Main Methods:
- Analysis of mRNA transcripts in alveolar macrophages using complementary DNA.
- Detection of PDGF-like mediator release from alveolar macrophages.
- In vitro differentiation of monocytes to study c-sis expression.
Main Results:
- Normal and diseased alveolar macrophages spontaneously expressed c-sis mRNA.
- These cells released a mediator with PDGF properties (chemotactic, mitogenic, receptor binding, antibody precipitation).
- Blood monocytes lacked c-sis mRNA, but expressed it upon differentiation into macrophages.
Conclusions:
- c-sis gene expression and PDGF production occur during monocyte to alveolar macrophage differentiation.
- PDGF produced by alveolar macrophages may contribute to normal lung defense mechanisms.
- The c-sis/PDGF pathway is implicated in lung inflammation processes.
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