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.
Highlights
Macrophages represent large, morphologically and functionally heterogeneous, immune cell population that is often regarded as a bridge between innate and adaptive immunity [1, 2]
In this paper we first evaluated the influence of recombinant banana lectin (rBanLec) stimulation on the functional characteristics of murine peritoneal resident (RMs) and thioglycollate-elicited macrophages (TGMs) in two genetically different inbred mouse strains BALB/c and C57BL/6; second, we identified rBanLec target membrane structures, TLR2 and CD14; and third, the functional effects of these interactions were examined in fine detail
The highest levels of O2- were recorded in non-stimulated RMs and TGMs cultures and in rBanLec-stimulated cultures its level negatively correlated to the applied rBanLec concentration (Fig 2B)
Summary
Macrophages represent large, morphologically and functionally heterogeneous, immune cell population that is often regarded as a bridge between innate and adaptive immunity [1, 2]. By acting as antigen-presenting cells, they exert an important role in initiation and shaping of the adaptive immune response [3]. Genetic background-dependent qualitative and quantitative differences in the macrophage responses to external stimuli are reported [9]. Depending primarily on their morphological characteristics, peritoneal macrophages, most often used as a model system in macrophages-related functional studies, are divided into two groups assigned as large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs). The SPMs are generally considered as more responsive to proinflammatory stimulation, it is difficult to associate a specific type of a response exclusively with LPMs or SPMs as the response to (re)stimulation depends on genetic background and environment
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