Lymphangiogenesis, Myeloid Cells and Inflammation

Lianping Xing; Rui-Cheng Ji

Disclosures

Expert Rev Clin Immunol. 2008;4(5):599-613. 

In This Article

Conclusion

Since the identification of LEC markers and LEC growth factors, and the development of invivo imaging tools to visualize lymphatic draining functions, the following findings have been made in the field of inflammatory lymphangiogenesis:

  • Both acute and chronic inflammation cause increased local and draining LN lymphangiogenesis;

  • Inflammatory cytokines stimulate myeloid lineage cells, such as macrophages and DCs, to produce and release lymphatic growth factors;

  • Eliminating of macrophages reduces inflammatory lymphangiogenesis;

  • Cells positive for the pan myeloid marker CD11b are present in newly formed lymphatic vasculature in the inflammatory area.

Based on these findings, we have proposed a model to explain the importance of the lymphatic system in the development and progression of inflammatory arthritis (Figure3). Joint inflammation recruits circulating CD11b+ myeloid cells from circulation. These cells produce lymphatic growth factors, such as VEGF-C, to stimulate lymphatic vessel formation. The functional lymphatic vessels transport inflammatory lymph-carrying inflammatory cells, catabolic factors and cytokines to the draining LNs and promote lymphangiogenesis, leading to an expansion of the LNs and dilation of the lymphatic sinuses containing inflammatory cells. Sufficient lymphatic drainage limits the degree of joint inflammation by removing catabolic cytokines from the interstitial space. This model emphasizes the importance of drainage and clearance function of the lymphatic system in limiting the progression of chronic inflammatory arthritis. However, whether or not the lymphatic system has a different impact on the pathogenesis of acute and chronic inflammation needs to be investigated in the future.

Figure 3.

The role of lymphatic vasculature and drainage in the pathologic process of inflammatory arthritis. (1) Angiogenesis occurs at a very early stage and provides support for an expansion of the inflammatory pannus. (2) Increased inflammatory cytokines and chemokines recruit circulating CD11b+ myeloid cells to joints. (3) CD11b+ cells produce VEGF-C in response to inflammatory signals and stimulate the formation of lymphatic vessels. (4) These functional vessels transport inflammatory lymph-carrying inflammatory cells, catabolic factors and cytokines to the draining popliteal lymph nodes. (5) Within the lymph nodes, cytokines stimulate CD11b+ cells to produce VEGF-C and promote lymphangiogenesis, leading to an expansion of the lymph nodes and dilation of lymphatic sinuses containing inflammatory cells. Sufficient lymphatic drainage limits the degree of joint inflammation. LYVE = Lymphatic vascular endothelial hyaluronan receptor; Tg = Transgenic.

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