Macrophages play crucial roles in protecting our bodies from infection and cancers. As macrophages are multi-functional immune cells, they have diverse plastic subsets, such as M1 and M2, derived from naïve M0 cells. Subset-specific macrophage probes are essential for deciphering and monitoring the various activation of macrophages, but developing such probes has been challenging. Here we report a fluorescent probe, CDr17, which is selective for M1 macrophages over M2 or M0. The selective staining mechanism of CDr17 is explicated as Gating-Oriented Live-cell Distinction (GOLD) through overexpressed GLUT1 in M1 macrophages. Finally, we demonstrate the suitability of CDr17 to track M1 macrophages in vivo in a rheumatoid arthritis animal model.

The differentiation of the distinct phenotypes of macrophages is essential for monitoring the stage of inflammatory diseases for accurate diagnosis and treatment. Recent studies revealed that the level of hypochlorite (OCl–) varies from activated M1 macrophages (killing pathogens) to M2 (resolution of inflammation) during inflammation. Thus, we developed a simple and efficient fluorescent probe for discriminating M1 from M0 and M2. Herein, fluorescent-based imaging is applied as an alternative to immunohistochemistry, which is challenging due to the tedious process and high cost. We developed a hypochlorite-specific probe PMS-T to differentiate M1 and M2, employing a metabolism-oriented live-cell distinction. This probe enables the detection of inflammatory rheumatoid arthritis in an ex vivo mouse model. Thus, it can be a potential chemical tool for monitoring inflammatory diseases, including rheumatoid arthritis, that may overcome the existing barriers of immunohistochemistry.

Human neutrophils are the most abundant leukocytes and have been considered as the first line of defence in the innate immune system. Selective imaging of live neutrophils will facilitate the in situ study of neutrophils in infection or inflammation events as well as clinical diagnosis. However, small‐molecule‐based probes for the discrimination of live neutrophils among different granulocytes in human blood have yet to be reported. Herein, we report the first fluorescent probe NeutropG for the specific distinction and imaging of active neutrophils. The selective staining mechanism of NeutropG is elucidated as metabolism‐oriented live‐cell distinction (MOLD) through lipid droplet biogenesis with the help of ACSL and DGAT. Finally, NeutropG is applied to accurately quantify neutrophil levels in fresh blood samples by showing a high correlation with the current clinical method.

Macrophages are the most plastic immune cells by changing their characters in response to environmental stimuli. Broadly, macrophages are categorized into two different subsets based on M1/M2 paradigm, which exhibit completely contrary phenotypes. Whereas M1 macrophages are aggressive to offend invaders such as bacteria and tumors, M2 are anti-inflammatory cells and seemingly help tumor immunity. Tumor-associated macrophages are typical examples of M2 cells as the key components of forming and maintaining the tumor microenvironment. Despite the intensive interest, monitoring M2 macrophages in real time is hampered by the lack of competent detection tools. Here, we report the first M2 selective probe CDg18 with a novel mechanism of gating-oriented live-cell distinction through M2-favored fatty acid transporters. To demonstrate the potential of CDg18, we visualize the progressive phenotypic change of M2 toward M1 using a resveratrol analogue HS-1793 as a reprogramming effector. Combined together with M1 probe CDr17, the diminishing M2 character and emerging M1 markers could be simultaneously monitored in real time through the multicolor changes during macrophage reprogramming.

Presently, the number of residing foreigners became over 1.1 million, reaching 2.2% out of total population. Compared with developed countries, though it is low percentage, when considering the increasing speed of incoming foreigners, low birth rate and aging, the transition to multicultural society is not our choice but necessity. An increase of female marriage immigrants in Korea is not only the result of population movement caused by super-national globalization but also in other side, proceeded with Korean demographic traits such as low birth rate, aging, inequality in sex rates, increased rate of spinsters and action of Korean women's values which is avoiding rural area. The rate of female marriage immigrants had largely increased from mid-1990's caused by amity with mainland china, and after 2000, most of cases were that women came from underdeveloped countries got married so called Korean dream of Korean nationality acquisition and upgrade of economic position and etc. through marriage as a means of escaping from poverty. Particularly, as men like bachelors in farming and fishing communities were excluded in marriages with Korean women due to the his economic level or cultural conditions, from 1995, government initiated the campaign “getting a bride for a rural bachelor” and consequently international marriages were further more increased. However, as disguised marriage problem with Korean Chinese women has become a serious social issue, in 2000's, trend is that international marriages with women came from underdeveloped countries like south-east Asian countries, Mongolia, Uzbekistan, etc. were increased, while international marriages with Korean Chinese women were decreased. For coexisting society with mutual respects among multi-races/multi-cultures, it is required that making immigrants have recognition of new citizen in Korean society as members of local community at the same time natives have recognition of comprehension and tolerance to agree and respect mutually other things not as wrong but as special ones. That is, It is required to promote awareness of new democratic citizenship recognizing positively differences, being different resulted from social-cultural diversities such as race, nation and religion, etc. emerging in multi-cultural society and regarding those as valuable and mutually respecting ones. We need to make female marriage immigrants to recognize their importance and necessity as political being in Korean political society and make foundation for them to live as proud democratic citizen in local community.