Table 1.
Effects of lymphatic vessel stimulation in inflammatory diseases.
| Animal model | Inflammatory stimulus | Method of lymphatic vasculature activation | Effects | References |
|---|---|---|---|---|
| SKIN INFLAMMATION | ||||
| K14-VEGF-A mice | Oxazolone | Transgenic VEGF-C delivery (crossed with K14-VEGF-C mice) | Reduced inflammatory edema and cell infiltration Expanded skin lymphatic vasculature Normalization of skin blood vasculature, epidermal differentiation and proliferation Improved lymphatic drainage function |
(28) |
| Local injection of recombinant VEGF-C156Ser | Reduced inflammatory edema Expanded skin lymphatic vasculature Normalization of skin blood vasculature Reduced inflammatory cell infiltration |
|||
| K14-VEGF-C mice | Injections of LPS or LTA and MDP | Transgenic VEGF-C delivery | Expanded lymphatic skin and LN vasculature Increased inflammatory cell migration to LNs Reduced inflammatory edema and erythema Faster antigen clearance |
(29) |
| TPA | Increased clearance of lymphatic-specific tracer | (30) | ||
| UVB irradiation | Reduced inflammatory edema and epidermal thickening Expanded lymphatic vasculature Improved lymphatic drainage function |
(31) | ||
| Oxazolone | Reduced inflammatory edema and epidermal thickening Expanded lymphatic vasculature Lower levels of IL-1β and VEGF-A |
|||
| K14-VEGF-D mice | UVB irradiation | Transgenic VEGF-D delivery | Reduced inflammatory edema and epidermal thickening Expanded lymphatic vasculature Improved lymphatic drainage function |
(31) |
| Oxazolone | Reduced inflammatory edema and epidermal thickening Expanded lymphatic vasculature |
|||
| Wildtype mice | UVB irradiation | Local injection of recombinant VEGF-C156Ser | Reduced inflammatory edema and cell infiltration Expanded lymphatic vasculature |
(32) |
| INFLAMMATORY BOWEL DISEASE | ||||
| Wildtype mice | DSS | Adenoviral delivery of VEGF-C | Reduced colitis severity and inflammatory cell infiltration Increased lymphatic vessel density and proliferation Improved lymphatic drainage function Increased inflammatory cell migration to LNs |
(33) |
| IL-10 knockout mice | Lack of anti-inflammatory IL-10 | |||
| RHEUMATOID ARTHRITIS | ||||
| TNF-α transgenic mice | TNF-α overexpression | Adeno-associated viral delivery of VEGF-C | Expanded lymphatic vasculature Reduced synovial volume, bone and cartilage erosion and osteoclast numbers Improved joint movement and lymphatic clearance function |
(34) |
| iNOS inhibition | Improved lymphatic clearance function Restored lymphatic contractions |
(35) | ||
DSS, dextran sulfate sodium; LN, lymph node; LPS, lipopolysaccharide; LTA, lipoteichoic acid; LV, lymphatic vessel; MDP, muramyl dipeptide; TPA, tetradecanoylphorbolacetate.