Lymphotoxin-alpha contributes to lymphangiogenesis.

ABSTRACT: Lymphotoxin-? (LT?), lymphotoxin-? (LT?), and tumor necrosis factor-? (TNF?) are inflammatory mediators that play crucial roles in lymphoid organ development. We demonstrate here that LT? also contributes to the function of lymphatic vessels and to lymphangiogenesis during inflammation. LT?(-/-) mice exhibited reduced lymph flow velocities and increased interstitial fluid pressure. Airways of LT?(-/-) mice infected with Mycoplasma pulmonis had significantly more lymphangiogenesis than wild type (WT) or LT?(-/-) mice, as did the skin draining immunization sites of LT?(-/-) mice. Macrophages, B cells, and T cells, known sources of LT and TNF?, were apparent in the skin surrounding the immunization sites as were LT?, LT?, and TNF? mRNAs. Ectopic expression of LT? led to the development of LYVE-1 and Prox1-positive lymphatic vessels within tertiary lymphoid organs (TLOs). Quantification of pancreatic lymphatic vessel density in RIPLT?LT?(-/-) and WT mice revealed that LT? was sufficient for inducing lymphangiogenesis and that LT? was not required for this process. Kidneys of inducible LT? transgenic mice developed lymphatic vessels before the appearance of obvious TLOs. These data indicate that LT? plays a significant role in lymphatic vessel function and in inflammation-associated lymphangiogenesis.

SUBMITTER: Mounzer RH 

PROVIDER: S-EPMC2951858 | biostudies-other | 2010 Sep

REPOSITORIES: biostudies-other