The purpose of this work was to report our initial experience with lymphaticovenular anastomoses (LVA), a controversial technique for lymphedema treatment. Although LVA technique was described many years ago, the procedure is not as widespread as it was supposed to be, taking into account the high impact that lymphedema has in the quality of life of patients. Thus, 12 patients, 5 with lower limb and 7 with upper limb lymphedema, underwent LVA surgery under local anesthesia. Two patients were excluded from the study due to the lack of follow-up. At 18 months, 8 out 10 patients showed a variable objective reduction of the perimeter of the limbs and 9 patients presented a subjective clinical improvement. These results joined to the outcomes of the most experienced surgeons in this field are encouraging, although there are still many issues that need to be addressed with research to optimize the efficacy of this technique.
Dendritic cell (DC) transmigration across the lymphatic endothelium is critical for the initiation and sustenance of immune responses. Under noninflammatory conditions, DC transit across the lymphatic endothelial cell (LEC) has been shown to be integrin independent. In contrast, there is increasing evidence for the participation of integrins and their ligands in DC transit across lymphatic endothelium under inflammation. In this sense, we describe the formation of ICAM-1 (CD54)-enriched three-dimensional structures on LEC/DC contacts, as these DCs adhere to inflamed skin lymphatic vessels and transmigrate into them. In vitro imaging revealed that under inflammation ICAM-1 accumulated on microvilli projections surrounding 60% of adhered DCs. In contrast, these structures were scarcely formed in noninflammatory conditions. Furthermore, ICAM-1-enriched microvilli were important in promoting DC transendothelial migration and DC crawling over the LEC surface. Microvilli formation was dependent on the presence of β-integrins on the DC side and on integrin conformational affinity to ligand. Finally, we observed that LEC microvilli structures appeared in close vicinity of CCL21 depots and that their assembly was partially inhibited by CCL21-neutralizing antibodies. Therefore, under inflammatory conditions, integrin ligands form three-dimensional membrane projections around DCs. These structures offer docking sites for DC transit from the tissue toward the lymphatic vessel lumen.
The deep inferior epigastric perforator (DIEP) flap has been shown to be a valid option for breast reconstruction, as it has certain advantages over the free TRAM flap, including lower morbidity in the donor area, conservation of abdominal wall function, and reduced postoperative pain. However, some cases of venous congestion in using the DIEP flap have been described. The authors present a case in which the venous return in a DIEP flap objectively (by measurement with a flux meter) presented a marked improvement (from 4 ml/min to 13.9 ml/min) after venous drainage was increased by means of the supplementary anastomosis of a comitant vein from the deep inferior epigastric pedicle to the intercostal branch of the internal mammary vein. The preservation of this branch is a simple and effective technique to improve the venous drainage of DIEP flaps, whether signs of congestion are present or not.
CD137/TNFR9/41BB was originally described as a surface molecule present on activated T and NK cells. However, its expression is broader among leukocytes, and it is also detected on hypoxic endothelial cells and inflamed blood vessels, as well as in atherosclerotic lesions. Here, we demonstrate that lymphatic endothelial cells (LECs) up-regulate CD137 expression from undetectable baseline levels on stimulation with TNF-α, LPS, and IL-1β. CD137 cross-linking with an agonistic mAb results in NF-κB nuclear translocation, followed by up-regulation of VCAM and a 3-fold increase in the production of the chemokine CCL21. Accordingly, there is a 50% increase in CCR7-dependent migration toward conditioned medium from activated LECs on CD137 cross-linking with the agonistic mAb or the natural ligand (CD137L). Such an enhancement of cell migration is also observed with monocyte-derived dendritic cells transmigrating across CD137-activated LEC monolayers. Using explanted human dermal tissue, we found that inflamed skin contains abundant CD137(+) lymphatic vessels and that ex vivo incubation of explanted human dermis with TNF-α induces CD137 expression in lymphatic capillaries. More interestingly, treatment with CD137 agonistic antibody induces CCL21 expression and DC accumulation close to lymphatic vessels. Collectively, our results demonstrate that the inflammatory function of lymphatic vessels can be regulated by CD137.
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