Rabbit Anti-ARG1 monoclonal antibody, clone TZ10-17

Nonylphenol (NP) as well-known "endocrine disrupter" influences sexual and reproductive development. Here, we investigated the effect of NP on M1-/M2-type macrophages and their role in lipopolysaccharide (LPS)-induced sepsis. Polarized macrophages of M1-and M2-types were obtained by the treatment with LPS and interleukin-4 (IL-4) to bone marrow-derived macrophages (BMDM), respectively. Coincubation of M1-macrophages with NP decreased COX-2, iNOS, IL-6, and TNF-alpha expression but no changes were detected in the production of nitric oxide (NO). Survival probability of LPS-induced sepsis mice was enhanced by the injection of NP-treated BMDM as compared to the injection of NP-untreated control BMDM. In the meanwhile, the expression of arginase 1(Arg1), a marker for M2-polarized macrophages was increased by the stimulation with LPS in BMDM. Arg1 expression was also enhanced by the treatment with IL-4 in BMDM, which was reduced by the coincubation with NP. Survival probability of LPS-induced sepsis mice was decreased by the injection of BMDM treated with IL-4 and NP as compared to the injection of IL-4-treated BMDM. It suggests that NP might inhibit macrophage function and the polarization to M2-macrophages. Taken together, data demonstrate that NP could differently affect immune responses of polarized macrophages resulted in the modulation of LPS-induced sepsis. (C) 2016 Wiley Periodicals, Inc.

The IGF-1 signaling pathway and IGF-1-dependent macrophage/endothelial cell crosstalk was found to be critical features of the vascular regenerative effect displayed by implanted methacrylic acid -co-isodecyl acrylate (MAA-co-IDA; 40% MM) coated disks in CD1 mice. Inhibition of IGF-1 signaling using AG1024 an IGF1-R tyrosine kinase inhibitor abrogated vessel formation 14 days after disk implantation in a subcutaneous pocket. Explanted tissue had increased arginase 1 expression and reduced iNOS expression consistent with the greater shift from "M1" ("pro-inflammatory") macrophages to "M2" ("pro-angiogenic") macrophages for MAA coated disks relative to control MM (methyl methacrylate-co-IDA) disks; the latter did not generate a vascular response and the polarization shift was muted with AG1024. In vitro, medium conditioned by macrophages (both human dTHP1 cells and mouse bone marrow derived macrophages) had elevated IGF-1 mRNA and protein levels, while the cells had reduced IGF1-R but elevated IGFBP-3 mRNA levels. These cells also had reduced iNOS and elevated Arg1 expression, consistent with the in vivo polarization results, including the inhibitory effects of AG1024. On the other hand, HUVEC exposed to dTHP1 conditioned medium migrated and proliferated faster suggesting that the primary target of the macrophage released IGF-1 was endothelial cells. Although further investigation is warranted, IGF-1 appears to be a key feature underpinning the observed vascularization. Why MM based materials have this effect remains to be defined, however. (C) 2017 Elsevier Ltd. All rights reserved.