Maggot secretions skew monocyte-macrophage differentiation away from a pro-inflammatory to a pro-angiogenic type

Mariena J A van der Plas; Jaap T van Dissel; Peter H Nibbering

doi:10.1371/journal.pone.0008071

Maggot secretions skew monocyte-macrophage differentiation away from a pro-inflammatory to a pro-angiogenic type

Mariena J A van der Plas, Jaap T van Dissel, Peter H Nibbering

41 Citations (Scopus)

Abstract

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 (MØ-1) and anti-inflammatory/pro-angiogenic macrophages (MØ-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 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-alpha, 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.

CONCLUSIONS: Maggot secretions skew the differentiation of monocytes into macrophages away from a pro-inflammatory to a pro-angiogenic type.

Original language	English
Journal	PLOS ONE
Volume	4
Issue number	11
Pages (from-to)	e8071
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0008071
Publication status	Published - 30 Nov 2009

Keywords

Animals
Cell Differentiation
Cytokines
Diptera
Flow Cytometry
Humans
Inflammation
Larva
Lipopolysaccharides
Lymphocytes
Macrophages
Monocytes
Neovascularization, Pathologic
Wound Healing
Journal Article
Research Support, Non-U.S. Gov't

Access to Document

10.1371/journal.pone.0008071

Cite this

@article{01f1e543dcbe4042ba95adb757dc70e7,

title = "Maggot secretions skew monocyte-macrophage differentiation away from a pro-inflammatory to a pro-angiogenic type",

abstract = "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 (M{\O}-1) and anti-inflammatory/pro-angiogenic macrophages (M{\O}-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 M{\O}-1 with a partial M{\O}-2-like morphology but lacking CD163, which is characteristic for M{\O}-2. In response to LPS or LTA, secretions-differentiated M{\O}-1 produced less pro-inflammatory cytokines (TNF-alpha, IL-12p40 and MIF) than control cells. Similar results were observed for M{\O}-2 when stimulated with low concentrations of LPS. Furthermore, secretions dose-dependently led to M{\O}-1 and M{\O}-2 characterized by an altered chemokine production. Secretions led to M{\O}-2, but not M{\O}-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.",

keywords = "Animals, Cell Differentiation, Cytokines, Diptera, Flow Cytometry, Humans, Inflammation, Larva, Lipopolysaccharides, Lymphocytes, Macrophages, Monocytes, Neovascularization, Pathologic, Wound Healing, Journal Article, Research Support, Non-U.S. Gov't",

author = "{van der Plas}, {Mariena J A} and {van Dissel}, {Jaap T} and Nibbering, {Peter H}",

year = "2009",

month = nov,

day = "30",

doi = "10.1371/journal.pone.0008071",

language = "English",

volume = "4",

pages = "e8071",

journal = "PLoS Computational Biology",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "11",

}

TY - JOUR

T1 - Maggot secretions skew monocyte-macrophage differentiation away from a pro-inflammatory to a pro-angiogenic type

AU - van der Plas, Mariena J A

AU - van Dissel, Jaap T

AU - Nibbering, Peter H

PY - 2009/11/30

Y1 - 2009/11/30

N2 - 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 (MØ-1) and anti-inflammatory/pro-angiogenic macrophages (MØ-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 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-alpha, 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.CONCLUSIONS: Maggot secretions skew the differentiation of monocytes into macrophages away from a pro-inflammatory to a pro-angiogenic type.

AB - 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 (MØ-1) and anti-inflammatory/pro-angiogenic macrophages (MØ-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 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-alpha, 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.CONCLUSIONS: Maggot secretions skew the differentiation of monocytes into macrophages away from a pro-inflammatory to a pro-angiogenic type.

KW - Animals

KW - Cell Differentiation

KW - Cytokines

KW - Diptera

KW - Flow Cytometry

KW - Humans

KW - Inflammation

KW - Larva

KW - Lipopolysaccharides

KW - Lymphocytes

KW - Macrophages

KW - Monocytes

KW - Neovascularization, Pathologic

KW - Wound Healing

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1371/journal.pone.0008071

DO - 10.1371/journal.pone.0008071

M3 - Journal article

C2 - 19956650

SN - 1932-6203

VL - 4

SP - e8071

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 11

ER -

Maggot secretions skew monocyte-macrophage differentiation away from a pro-inflammatory to a pro-angiogenic type

Abstract

Keywords

Access to Document

Fingerprint

Cite this