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Macrophages and the activity of high endothelial venules. The effect of interferon-gamma
R E Mebius1, H R Hendriks, J Brevé
1Department of Cell Biology, Medical Faculty, Vrije Universiteit, Amsterdam, The Netherlands.
Abstract:
Interruption of the afferent lymphatic vessels of rat popliteal lymph nodes led to the disappearance of the monoclonal antibody ED3-reactive subcapsular sinus macrophages within 3 weeks, but had no effect on the ED1+ macrophages in the paracortical area. This disconnection of the afferent lymph flow to the popliteal lymph node also reduced the capacity of high endothelial venules (HEV) to bind lymphocytes and led to a flattening of the HEV. Activating factors or cells in the incoming lymph might be responsible for the maintenance and function of several different cell populations and we therefore wished to determine if the effects of interruption could be restored by injection of recombinant rat interferon-gamma (rIFN-gamma). Injection of rIFN-gamma directly into operated lymph nodes could mediate an apparent increase of ED1+ cells within 24 h but rIFN-gamma could not restore the macrophage subpopulation in the subcapsular sinus, as recognized by monoclonal antibody ED3. Restoration of the decreased binding capacity of HEV could not be observed with the doses and time points tested, suggesting that HEV are a distinct type of endothelium.
Insights
Disrupting lymphatic vessels in rat lymph nodes eliminated subcapsular sinus macrophages but spared paracortical ones. Recombinant rat interferon-gamma (rIFN-gamma) partially restored cell populations but not high endothelial venule function.
Area of Science:
- Immunology
- Lymphatic System Biology
Background:
- Afferent lymphatic vessels deliver crucial factors to lymph nodes.
- Subcapsular sinus macrophages and high endothelial venules (HEV) are vital for immune function.
- The role of lymph-borne factors in maintaining these structures is not fully understood.
Purpose of the Study:
- To investigate the impact of afferent lymphatic vessel interruption on lymph node cellularity and HEV function.
- To determine if recombinant rat interferon-gamma (rIFN-gamma) can restore lymph node homeostasis after lymphatic interruption.
Main Methods:
- Surgical interruption of afferent lymphatic vessels in rat popliteal lymph nodes.
- Immunohistochemical analysis using ED1 and ED3 monoclonal antibodies to identify macrophage populations.
- Assessment of high endothelial venule (HEV) lymphocyte binding capacity.
- Intranodal injection of rIFN-gamma to evaluate its restorative effects.
Main Results:
- Interruption of afferent lymphatics caused the disappearance of ED3+ subcapsular sinus macrophages within 3 weeks.
- ED1+ macrophages in the paracortical area remained unaffected.
- Lymphatic disconnection reduced HEV lymphocyte binding capacity and caused HEV flattening.
- rIFN-gamma injection transiently increased ED1+ cells but did not restore ED3+ macrophages or HEV function.
Conclusions:
- Afferent lymph flow is essential for maintaining subcapsular sinus macrophage populations.
- rIFN-gamma partially influences macrophage populations but cannot fully restore lymph node architecture or HEV function.
- HEV appear to be a distinct endothelial type with unique maintenance requirements, independent of lymph-borne activating factors tested.
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