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

Abstract

BackgroundMaggots 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 (MØ-1) and anti-inflammatory/pro-angiogenic macrophages (MØ-2) as these cells play a central role in wound healing.Methodology/Principal FindingsFreshly 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 MØ-1 with a partial MØ-2-like morphology but lacking CD163, which is characteristic for MØ-2. In response to LPS or LTA, secretions-differentiated MØ-1 produced less pro-inflammatory cytokines (TNF-α, IL-12p40 and MIF) than control cells. Similar results were observed for MØ-2 when stimulated with low concentrations of LPS. Furthermore, secretions dose-dependently led to MØ-1 and MØ-2 characterized by an altered chemokine production. Secretions led to MØ-2, but not MØ-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.ConclusionsMaggot secretions skew the differentiation of monocytes into macrophages away from a pro-inflammatory to a pro-angiogenic type.

Myeloid Angiogenic Cells Act as Alternative M2 Macrophages and Modulate Angiogenesis through Interleukin-8

“…Whereas MACs had a spindle, elongated shape, M1 macrophages showed distinctively flat, "fried-egg-like" morphology. These two contrasting macrophage morphologies have been described previously (31) and are related to M2 and M1 phenotypes, respectively. D 1 7 ( 9 -1 0 ) 1 0 4 5 -1 0 5 Figure 3.…”

Housefly Maggots (Musca domestica) Protein-enriched Fraction/ extracts (PE) Inhibit Lipopolysaccharide-induced Atherosclerosis Pro-inflammatory Responses

“…The role of antimicrobial peptides acting as anti-inflammatory factors directly or indirectly has been accepted by many researchers 33,34) . These results were also in agreement with previous studies reporting the suppressive effect of maggot excretions/secretions on human multiple neutrophil pro-inflammatory responses 4,6) . Hou L found that an extract of housefly larvae had antibacterial and anti-tumor functions in vitro 35) .…”

“…Recent studies have shown that homogenate product from maggots can promote wound nerve regeneration within a murine cutaneous wound model 32) . The beneficial effects of maggots on chronic wounds may be explained in part by the inhibition of multiple pro-inflammatory responses 6) . In the present study, we also performed a pre-experiment on macrophages to test the concentration of IL-1 .…”

“…They provide useful information for the development of anti-tumor drugs 4) and have also been used in functional food for many centuries. Recent studies in vitro have shown that maggot secretions suppressed pro-inflammatory responses of human monocytes through the upregulation of cyclic AMP 5) and also could skew the differentiation of monocytes into macrophages from a pro-inflammatory to a pro-angiogenic type 6) . Another study reported that maggot excretions/secretions potently inhibited multiple neutrophil pro-inflammatory responses, including chemotaxis, degranulation, respiratory burst and integrin expression, without affecting the antimicrobial activities of neutrophils 7) .…”

Oncomodulin and macrophages derived factors in pancreas injury and development paradigms

“…Therefore it is not surprising that in the present study activated macrophage conditioned medium factors is detrimental to embryonic pancreas explants growth in culture. The relative healthy growth of embryonic pancreas explants cultured with non activated macrophage conditioned medium and its increased Pdx-1 expression could be explained by growth factors constitutively secreted by non activated macrophages as demonstrated in a number of publication [18][19][20]. We speculate that in cultures with zymosan treated macrophages-conditioned medium, macrophages growth-promoting effect is masked by the much powerful cytotoxic effect.…”