Neutrophil granule proteins tune monocytic cell function

Soehnlein, Oliver; Weber, Christian; Lindbom, Lennart

doi:10.1016/j.it.2009.06.006

Cited by 145 publications

(107 citation statements)

References 105 publications

(109 reference statements)

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“…Granule proteins released by activated neutrophils regulate macrophage function (40). Specifically, NE activates TLR4 (41) and induces leishmanicidal activity through TLR4 (31).…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory Clearance of Apoptotic Neutrophils Induces an IL-12lowIL-10high Regulatory Phenotype in Macrophages

Filardy

Pires

Nunes

et al. 2010

The Journal of Immunology

200

152

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Clearance of apoptotic exudate neutrophils (efferocytosis) induces either pro- or anti-inflammatory responses in mouse macrophages depending on host genetic background. In this study, we investigated whether neutrophil efferocytosis induces a stable macrophage phenotype that could be recalled by late restimulation with LPS. Bone marrow-derived macrophages previously stimulated by pro- but not anti-inflammatory neutrophil efferocytosis expressed a regulatory/M2b phenotype characterized by low IL-12 and high IL-10 production following restimulation, increased expression of LIGHT/TNF superfamily 14, Th2-biased T cell responses, and permissive replication of Leishmania major. Induction of regulatory/M2b macrophages required neutrophil elastase activity and was partially dependent on TLR4 signaling. These results suggested that macrophage differentiation to a regulatory phenotype plays a role in resolution of inflammation but could contribute to increased humoral Ab responses and parasite persistence in the infected host.

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“…Granule proteins released by activated neutrophils regulate macrophage function (40). Specifically, NE activates TLR4 (41) and induces leishmanicidal activity through TLR4 (31).…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory Clearance of Apoptotic Neutrophils Induces an IL-12lowIL-10high Regulatory Phenotype in Macrophages

Filardy

Pires

Nunes

et al. 2010

The Journal of Immunology

200

152

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“…These macrophages may be effective in recruiting and activating other leukocytes resulting in the enhanced clearance of the infection. For example, LL-37 can activate macrophages to produce inflammatory cytokines in response to microbial stimuli and induce efficient phagocytosis of IgGopsonized bacteria (40). The peptide can modulate the differentiation of monocytes to DCs that promote the development of a Th subset expressing high levels of IFN-g and low/undetectable levels of IL-4/IL-5 (18), although maturation of the LL-37-differentiated DCs by several TLR ligands may be suppressed (19).…”

Section: Discussionmentioning

confidence: 99%

LL-37 Directs Macrophage Differentiation toward Macrophages with a Proinflammatory Signature

Does

Beekhuizen

Ravensbergen

et al. 2010

The Journal of Immunology

158

118

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The human cathelicidin LL-37 has broad-spectrum antimicrobial activity. It also participates at the interface of innate and adaptive immunity by chemoattracting immune effector cells, modulating the production of a variety of inflammatory mediators by different cell types, and regulating the differentiation of monocytes into dendritic cells. In this study, we investigated the effects of LL-37 on the differentiation of human monocytes into anti-inflammatory macrophages (MΦ-2; driven by M-CSF) versus proinflammatory macrophages (MΦ-1; driven by GM-CSF) as well as on fully differentiated MΦ-1 and MΦ-2. Results revealed that monocytes cultured with M-CSF in the presence of LL-37 resulted in macrophages displaying a proinflammatory signature, namely, low expression of CD163 and little IL-10 and profound IL-12p40 production on LPS stimulation. The effects of LL-37 on M-CSF-driven macrophage differentiation were dose- and time-dependent with maximal effects observed at 10 μg/ml when the peptide was present from the start of the cultures. The peptide enhanced the GM-CSF–driven macrophage differentiation. Exposure of fully differentiated MΦ-2 to LL-37 for 6 d resulted in macrophages that produced less IL-10 and more IL-12p40 on LPS stimulation than control MΦ-2. In contrast, LL-37 had no effect on fully differentiated MΦ-1. Peptide mapping using a set of 16 overlapping 22-mer peptides covering the complete LL-37 sequence revealed that the C-terminal portion of LL-37 is responsible for directing macrophage differentiation. Our results furthermore indicate that the effects of LL-37 on macrophage differentiation required internalization of the peptide. Together, we conclude that LL-37 directs macrophage differentiation toward macrophages with a proinflammatory signature.

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“…28,29 Traditionally, these granules have been regarded as being packaged with potent antibacterial enzymes and peptides. It is now clear that the collection of proteins encompasses other functions as well (e.g., facilitating the adhesion of monocytes to the endothelium), being packaged into 3 classes of granules (1 , 2 , 3 ).…”

Section: Cytoplasmic Granule Proteinsmentioning

confidence: 99%

Transcriptomes reflect the phenotypes of undifferentiated, granulocyte and macrophage forms of HL-60/S4 cells

Welch

Jauch

Langowski

et al. 2017

Nucleus

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To understand the chromatin changes underlying differential gene expression during induced differentiation of human leukemic HL-60/S4 cells, we conducted RNA-Seq analysis on quadruplicate cultures of undifferentiated, granulocytic-and macrophage-differentiated cell forms. More than half of mapped genes exhibited altered transcript levels in the differentiated cell forms. In general, more genes showed increased mRNA levels in the granulocytic form and in the macrophage form, than showed decreased levels. The majority of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in genes that exhibited differential transcript levels after either RA or TPA treatment. Changes in transcript levels for groups of genes with characteristic protein phenotypes, such as genes encoding cytoplasmic granular proteins, nuclear envelope and cytoskeletal proteins, cell adhesion proteins, and proteins involved in the cell cycle and apoptosis illustrate the profound differences among the various cell states. In addition to the transcriptome analyses, companion karyotyping by M-FISH of undifferentiated HL-60/S4 cells revealed a plethora of chromosome alterations, compared with normal human cells. The present mRNA profiling provides important information related to nuclear shape changes (e.g., granulocyte lobulation), deformability of the nuclear envelope and linkage between the nuclear envelope and cytoskeleton during induced myeloid chromatin differentiation.

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Neutrophil granule proteins tune monocytic cell function

Cited by 145 publications

References 105 publications

Proinflammatory Clearance of Apoptotic Neutrophils Induces an IL-12lowIL-10high Regulatory Phenotype in Macrophages

Proinflammatory Clearance of Apoptotic Neutrophils Induces an IL-12lowIL-10high Regulatory Phenotype in Macrophages

LL-37 Directs Macrophage Differentiation toward Macrophages with a Proinflammatory Signature

Transcriptomes reflect the phenotypes of undifferentiated, granulocyte and macrophage forms of HL-60/S4 cells

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