Maggot Secretions Skew Monocyte-Macrophage Differentiation Away from a Pro-Inflammatory to a Pro-Angiogenic Type

被引:41
|
作者
van der Plas, Mariena J. A. [1 ,2 ]
van Dissel, Jaap T. [1 ]
Nibbering, Peter H. [1 ]
机构
[1] Leiden Univ, Med Ctr, Dept Infect Dis, Leiden, Netherlands
[2] Leiden Univ, Med Ctr, Dept Surg, Leiden, Netherlands
来源
PLOS ONE | 2009年 / 4卷 / 11期
关键词
DIABETIC FOOT ULCERS; MIGRATION INHIBITORY FACTOR; APOPTOTIC CELLS; CYCLIC-AMP; INNATE IMMUNITY; CHRONIC WOUNDS; LEG ULCERS; CYTOKINE; THERAPY; EXPRESSION;
D O I
10.1371/journal.pone.0008071
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. Earlier we reported maggot secretions to inhibit pro-inflammatory responses of human monocytes. The aim of this study was to investigate the effect of maggot secretions on the differentiation of monocytes into pro-inflammatory (MO-1) and anti-inflammatory/proangiogenic macrophages (MO-2) as these cells play a central role in wound healing. Methodology/Principal Findings: Freshly isolated monocytes were incubated with secretions and GM-CSF or M-CSF for 6 days and then stimulated with LPS or LTA for 18 h. The expression of cell surface molecules and the levels of cytokines, chemokines and growth factors in supernatants were measured. Our results showed secretions to affect monocyte-macrophage differentiation leading to MO-1 with a partial MO-2-like morphology but lacking CD163, which is characteristic for MO-2. In response to LPS or LTA, secretions-differentiated MO-1 produced less pro-inflammatory cytokines (TNF-alpha, IL-12p40 and MIF) than control cells. Similar results were observed for MO-2 when stimulated with low concentrations of LPS. Furthermore, secretions dose-dependently led to MO-1 and MO-2 characterized by an altered chemokine production. Secretions led to MO-2, but not MO-1, producing enhanced levels of the growth factors bFGF and VEGF, as compared to control cells. The expression of cell-surface receptors involved in LPS/LTA was enhanced by secretions, that of CD86 and HLA-DR down-regulated, while receptors involved in phagocytosis remained largely unaffected. Conclusions: Maggot secretions skew the differentiation of monocytes into macrophages away from a pro-inflammatory to a pro-angiogenic type.
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页数:10
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