Modulation of functional characteristics of resident and thioglycollate-elicited peritoneal murine macrophages by a recombinant banana lectin

PLoS One. 2017 Feb 24;12(2):e0172469. doi: 10.1371/journal.pone.0172469. eCollection 2017.

Abstract

We demonstrated that a recombinant banana lectin (rBanLec), which structural characteristics and physiological impacts highly resemble those reported for its natural counterparts, binds murine peritoneal macrophages and specifically modulates their functional characteristics. By using rBanLec in concentrations ranging from 1 μg to 10 μg to stimulate resident (RMs) and thioglycollate-elicited (TGMs) peritoneal macrophages from BALB/c and C57BL/6 mice, we have shown that effects of rBanLec stimulation depend on its concentration but also on the functional status of macrophages and their genetic background. rBanLec, in a positive dose-dependent manner, promotes the proliferation of TGMs from both BALB/c and C57BL/6 mice, while its mitogenic influence on RMs is significantly lower (BALB/c mice) or not detectable (C57BL/6 mice). In all peritoneal macrophages, irrespective of their type and genetic background, rBanLec, in a positive dose dependent manner, enhances the secretion of IL-10. rBanLec stimulation of RMs from both BALB/c and C57BL/6 resulted in a positive dose-dependent promotion of proinflammatory phenotype (enhancement of NO production and IL-12 and TNFα secretion, reduction of arginase activity). Positive dose-dependent skewing toward proinflammatory phenotype was also observed in TGMs from C57BL/6 mice. However, the enhancement of rBanLec stimulation promotes skewing of TGMs from BALB/c mice towards anti-inflammatory profile (reduction of NO production and IL-12 secretion, enhancement of arginase activity and TGFβ and IL-4 secretion). Moreover, we established that rBanLec binds oligosaccharide structures of TLR2 and CD14 and that blocking of signaling via these receptors significantly impairs the production of TNFα and NO in BALB/c macrophages. Since the outcome of rBanLec stimulation depends on rBanLec concentration as well as on the functional characteristics of its target cells and their genetic background, further studies are needed to investigate its effects under physiological and specific pathological conditions.

MeSH terms

  • Animals
  • Arginase / genetics
  • Arginase / immunology
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Immunologic
  • Gene Expression Regulation
  • Immunologic Factors / pharmacology*
  • Interleukin-10 / agonists
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology*
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharide Receptors / immunology
  • Macrophage Activation / drug effects
  • Macrophages, Peritoneal / cytology
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / immunology
  • Plant Lectins / pharmacology*
  • Protein Binding
  • Recombinant Proteins / pharmacology
  • Signal Transduction
  • Thioglycolates / pharmacology*
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / immunology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • BanLec-I
  • IL10 protein, mouse
  • Immunologic Factors
  • Lipopolysaccharide Receptors
  • Plant Lectins
  • Recombinant Proteins
  • Thioglycolates
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Nitric Oxide
  • 2-mercaptoacetate
  • Arginase

Grants and funding

This research was funded by the Ministry of Education, Science, and Technological Development of the Republic of Serbia (grant number 172049) (http://www.mpn.gov.rs/). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.