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Infiltration of M2‐polarized macrophages in infected lymphatic malformations: possible role in disease progression
Author(s) -
Zhang W.,
He K.F.,
Yang J.G.,
Ren J.G.,
Sun Y.F.,
Zhao J.H.,
Zhao Y.F.
Publication year - 2016
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.14471
Subject(s) - lymphatic system , lymphatic endothelium , pathology , infiltration (hvac) , macrophage , cd68 , vascular endothelial growth factor , cd20 , immunohistochemistry , m2 macrophage , biology , immunology , medicine , cancer research , materials science , biochemistry , vegf receptors , in vitro , composite material
Summary Background Lymphatic malformations ( LM s), slow‐flow vascular anomalies resulting from abnormal development of lymphatic channels, often progress rapidly after trauma or infection. Objectives To explore the possible mechanism by which local infection promotes the progression of LM s. Methods Immunohistochemistry in serial sections and immunofluorescence were performed to label polarized macrophages. Tertiary lymphoid organs ( TLO s) in LM s were identified using antibodies against CD 3 (a T‐cell marker), CD 20 (a B‐cell marker) and PNA d (a high endothelial venule marker). Pearson's correlation and cluster analysis were carried out to delineate the relationship between macrophage infiltration and TLO formation. Rat models of LM were established to examine the role of lipopolysaccharide in LM development. Results Compared with normal skin tissues, both M1‐ and M2‐polarized macrophages were prevalent in LM s. Moreover, M2‐polarized macrophages were significantly increased in infected LM s with an elevated density of TLO s. M2‐polarized macrophages were observed in the centre of TLO s accompanied by intensive staining of macrophage colony‐stimulating factor, a strong chemotactic factor for monocytes/macrophages, suggesting that macrophages might be recruited through TLO s. Cluster analysis and Pearson's correlation suggested a close relationship between macrophage infiltration and TLO formation. Furthermore, the expression of CD 68 was also correlated with that of vascular endothelial growth factor ( VEGF )‐C and Ki67. Importantly, in an established LM rat model, lipopolysaccharide promoted the progression of the malformations with increased macrophage infiltration and TLO formation. Conclusions M2‐polarized macrophages that may be recruited through TLO s in infected LM s may contribute to the progression of the disease by secreting VEGF ‐C, and therefore accelerating the proliferation of lymphatic endothelial cells.