Endogenous calcitonin gene-related peptide deficiency exacerbates postoperative lymphedema by suppressing lymphatic capillary formation and M2 macrophage accumulation.

In this study, CGRP knockout (-/-) mice were used to show the actions of endogenous CGRP in postoperative lymphedema. After generating a mouse postoperative tail lymphedema model, the edema was observed to be more severe in CGRP-/- than wild-type mice. Numbers of LYVE-1-positive lymphatic capillaries were decreased and lymphatic capillary formation-related factors were down-regulated in CGRP-/- mice. In addition, accumulation of M2, but not M1 macrophages was selectively reduced in the edematous tissue of CGRP-/- mice. Selective depletion of M2 macrophages decreased lymphatic capillary formation and worsened lymphedema in wild-type mice but not CGRP-/- mice, where numbers of M2 macrophages were already diminished. These findings suggest that endogenous CGRP acts to ameliorate postoperative lymphedema by enhancing lymphatic capillary formation and M2 macrophages play critical roles. CGRP may be a useful therapeutic target for the treatment of postoperative lymphedema.
PMID: 31541644 [PubMed - as supplied by publisher]

Source: The American Journal of Pathology - September 17, 2019 Category: Pathology Authors: Matsui S, Tanaka M, Kamiyoshi A, Sakurai T, Ichikawa-Shindo Y, Kawate H, Dai K, Cui N, Wei Y, Tanaka M, Kakihara S, Nakamura K, Yamauchi A, Ishida K, Tanaka S, Kawamata M, Shindo T Tags: Am J Pathol Source Type: research