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Dacron stimulation of macrophage transforming growth factor-beta release
H P Greisler1, D Petsikas, D J Cziperle
1Loyola University Medical Center, Department of Surgery, Maywood, Illinois, USA.
Abstract:
This study evaluated the effect of Dacron on the release of macrophage transforming growth factor-beta (TGF-beta),an endothelial cell growth inhibitor. Rabbit peritoneal macrophages were grown in minimum essential medium (MEM) with 10% fetal bovine serum (FBS) in the presence or absence of Dacron (0.5 mm x 3 mm particles). Media were collected three times each week for 7 weeks. For the TGF-beta bioassay, mink lung epithelial cells (CCL64) were grown in MEM with 10% FBS. Test-conditioned media, 100 mu 1, were added (n = 4), and incubated 48 h. 3(H)-Thymidine (3(H)-TdR) uptake was determined and compared with 3(H)-TdR uptake using known pure TGF-beta standards. Media samples were additionally pre-incubated with a neutralizing anti-TGF-beta(1) antibody and the 3(H)-TdR uptake again quantitated. TGF-beta activity in the conditioned media of macrophages exposed to Dacron exceeded the control media groups in all weeks, reaching significance (P<0.05) in weeks 3, 4,5, 6 and 7. Pre-incubation of media samples with the anti-TGF-beta antibody inhibited this TGF-beta activity in all weeks with statistical significance in weeks 1, 2, 3, 5 and 7. The inhibitory effects of Dacron on endothelialization may be explained by the Dacron-induced release of TGF-beta from macrophages.
Insights
Dacron material significantly increases the release of macrophage transforming growth factor-beta (TGF-beta), a substance that inhibits endothelial cell growth. This explains Dacron's negative impact on endothelialization.
Area of Science:
- Biomaterials Science
- Cell Biology
- Immunology
Background:
- Macrophage-derived transforming growth factor-beta (TGF-beta) is a potent inhibitor of endothelial cell proliferation.
- The interaction between biomaterials and macrophages can influence the local cellular microenvironment.
Purpose of the Study:
- To investigate the effect of Dacron on the release of TGF-beta by macrophages.
- To determine if Dacron-induced TGF-beta release contributes to impaired endothelialization.
Main Methods:
- Rabbit peritoneal macrophages cultured with or without Dacron particles.
- Collection of conditioned media over 7 weeks.
- TGF-beta bioassay using mink lung epithelial cells and [3H]-thymidine uptake.
- Neutralization of TGF-beta with a specific antibody.
Main Results:
- Macrophage cultures exposed to Dacron showed significantly elevated TGF-beta activity compared to controls from week 3 to 7.
- Anti-TGF-beta antibody pre-incubation significantly reduced TGF-beta activity in Dacron-exposed cultures across multiple weeks.
- Dacron exposure consistently induced higher TGF-beta levels throughout the 7-week study period.
Conclusions:
- Dacron material stimulates macrophages to release increased amounts of TGF-beta.
- The elevated TGF-beta release by macrophages in response to Dacron likely underlies the observed inhibitory effects on endothelial cell growth and endothelialization.