| First Author | Mounzer RH | Year | 2010 |
| Journal | Blood | Volume | 116 |
| Issue | 12 | Pages | 2173-82 |
| PubMed ID | 20566898 | Mgi Jnum | J:164499 |
| Mgi Id | MGI:4834061 | Doi | 10.1182/blood-2009-12-256065 |
| Citation | Mounzer RH, et al. (2010) Lymphotoxin-alpha contributes to lymphangiogenesis. Blood 116(12):2173-82 |
| abstractText | Lymphotoxin-alpha (LTalpha), lymphotoxin-beta (LTbeta), and tumor necrosis factor-alpha (TNFalpha) are inflammatory mediators that play crucial roles in lymphoid organ development. We demonstrate here that LTalpha also contributes to the function of lymphatic vessels and to lymphangiogenesis during inflammation. LTalpha(-/-) mice exhibited reduced lymph flow velocities and increased interstitial fluid pressure. Airways of LTbeta(-/-) mice infected with Mycoplasma pulmonis had significantly more lymphangiogenesis than wild type (WT) or LTalpha(-/-) mice, as did the skin draining immunization sites of LTbeta(-/-) mice. Macrophages, B cells, and T cells, known sources of LT and TNFalpha, were apparent in the skin surrounding the immunization sites as were LTalpha, LTbeta, and TNFalpha mRNAs. Ectopic expression of LTalpha led to the development of LYVE-1 and Prox1-positive lymphatic vessels within tertiary lymphoid organs (TLOs). Quantification of pancreatic lymphatic vessel density in RIPLTalphaLTbeta(-/-) and WT mice revealed that LTalpha was sufficient for inducing lymphangiogenesis and that LTbeta was not required for this process. Kidneys of inducible LTalpha transgenic mice developed lymphatic vessels before the appearance of obvious TLOs. These data indicate that LTalpha plays a significant role in lymphatic vessel function and in inflammation-associated lymphangiogenesis. |
