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Introduction Molecular biomarkers of monocytes/macrophages identified to date have provided advanced diagnostic capabilities. We have accumulated a large amount of knowledge related to the role of innate immune response in the development of postinfarction cardiac remodeling. However, there is no significant advancement in clinical studies. Purpose The purpose was to assess prospects of macrophage biomarkers in diagnostics of postinfarction tissue inflammation associated with adverse cardiac remodeling in patients with myocardial infarction (MI). Methods The study included 41 patients with MI type 1, died in 2013–2014. We used a biobank of tissue samples for analysis. Group 1 (n=24) comprised patients who died within 72 hours of MI (the inflammatory phase), group 2 (n=17) comprised patients who died 4–28 days after MI (the regenerative phase). Macrophage infiltration in the heart was assessed by double immunofluorescence. We used stabilin-1 as a marker of M2 macrophages, while α-smooth muscle actin (α-SMA) was considered as a marker of cell transdifferentiation. Cells were counted in the infarct (IA) and non-infarct area (NIA). Morphological determination of adverse cardiac remodeling was based on the ratio of heart size, in particular, length/width ratio that was Results We identified subpopulations of stabilin-1+/α-SMA− and stabilin-1+/α-SMA+ macrophages. In the IA the number of stabilin-1+/α-SMA− macrophages was lower during the inflammatory phase than during the regenerative phase (Table 1). The calculation of sensitivity and specificity of stabilin-1+/α-SMA− macrophages in the NIA for predicting of adverse cardiac remodeling has shown following: AUC=0.96, p Conclusions We identified that number of stabilin-1+/α-SMA− macrophages in the NIA ranged from 0 to 18 cells/mm2 was associated with adverse cardiac remodeling. The presence of stabilin-1+/α-SMA+ macrophages could indicate persistent tissue inflammation and possibility of macrophage transdifferentiation and plasticity. Our study supports prospects for implementation of macrophage biomarkers in clinical practice that might become a breakthrough in the development of new methods for management of MI and following complications. Figure 1 Funding Acknowledgement Type of funding source: None

Investigation of the role of macrophages and their functional plasticity in reparative process accompanying myocardial infarction (MI) and postinfarction cardiac remodeling is the relevant issue of current medical science. The purpose of the study: to investigate CD68+ and stabilin-1 +-macrophage infiltration and its dynamics in patients with MI in comparison with intact myocardium. The study included patients with fatal MI type 1 (n=41). All patients were divided into 4 groups depending on the onset of death (group 1, n=13, patients who died during the first 24 hours of MI; group 2, n=11, patients who died within 24-72 hours of MI; group 3, n=9, patients who died on days 4-10; and group 4, n=8, patients who died 11-28 days after MI). The control group included patients (n=9) who died due to fatal trauma and who did not suffer from cardiovascular pathology. For evaluation of functional immunopheno-type of macrophages we used immunohistochemistry. We counted cells expressing on their surface a common macrophages marker - CD68 and specific marker of regulatory M2 macrophages that demonstrates an anti-inflammatory activity - stabilin-1 in the infarct area, peri-infarct area, and non-infarct area. In comparison with the intact myocardium (control group) the number of CD68+-macrophages in the infarct area, periinfarct area, and non-infarct area increased from the first day of disease and peaked on day 4-10. The quantity of stabilin-1 + macrophages in all zones investigated during the acute phase of MI was lower than in the intact myocardium and increased on day 4-10 in the infarct area. Furthermore, in the non-infarct zone the quantity of stabilin-1 +-macrophages was lower than its quantity in the control group both during the acute phase and the regenerative phase of MI. The data obtained indicate the participation of stabilin-1 + macrophages in process of postinfarction myocardial healing and the development of the inflammatory immune response in the myocardium during the acute phase of MI and its maintaining at late stages of the disease.

Background This study's aim was to identify CD68 and stabilin-1 expressions and their prognostic implications in patients with oral cavity cancer (OCC). Methods Stabilin-1 and CD68 immunochemical staining was conducted in samples from patients with OCC who underwent curative surgery in our institute. We retrospectively analyzed patients' clinical information. We investigated the relationship between CD68 and stabilin-1 expression levels and their effect on prognostic factors and survival. Results Fifty-four patients' data were analyzed. CD68 and stabilin-1 expressions were positively correlated (P = .008). CD68 and stabilin-1 expressions were not correlated with other prognostic factors (eg, T classification or lymph node metastasis). Stabilin-1 expression and tumor recurrence risk were positively correlated (P = .015). CD68 expression was neither associated with recurrence-free nor OCC-specific survival. Conclusion CD68 and stabilin-1 expressions in OCC were positively correlated. Stabilin-1 expression was significantly associated with OCC recurrence risk, but the prognostic value of CD68 was not confirmed.

Marianne B Ariganello,1,* Dainelys Guadarrama Bello,1,* Alejandra Rodriguez-Contreras,1 Shayan Sadeghi,1 Gaetano Isola,1 Fabio Variola,2,3 Antonio Nanci1,4 1Laboratory for the Study of Calcified Tissues and Biomaterials, Department of Stomatology, Faculty of Dental Medicine, Université de Montréal, Montreal, QC, Canada; 2Department of Mechanical Engineering, University of Ottawa, Ottawa, ON, Canada; 3Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada; 4Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada *These authors contributed equally to this work Background: Nanoscale surface modifications are widely touted to improve the biocompatibility of medically relevant materials. Immune cells, such as macrophages, play a critical role in the initial healing events following implantation. Methods: To understand the response of macrophages to nanotopography better, we exposed U937-derived macrophages to a distinctive mesoporous titanium surface (TiNano) produced by a process of simple chemical nanocavitation, and to mechanically polished titanium (TiPolished) and glass coverslip (Glass) surfaces as controls. Cell numbers and morphology were evaluated. Osteopontin expression and that of the proinflammatory SPARC protein and its stabilin 1 receptor were analyzed. Release of inflammation-associated cytokines and chemokines was also measured. Results: Compared to the two control surfaces, there were fewer U937 cells on TiNano, and these exhibited a more rounded morphology with long filopodia. The cells showed areas of punctate actin distribution, indicating formation of podosomes. Of the three proteins examined, only osteopontin’s immunofluorescence signal was clearly reduced. Irrespective of the substrate, the cytokine assay revealed important variations in expression levels of the multiple molecules analyzed and downregulation in a number of chemokines by the TiNano surface. Conclusion: These results indicate that macrophages sense and respond to the physicochemical cueing generated by the nanocavitated surface, triggering cellular and molecular changes consistent with lesser inflammatory propensity. Given the previously reported beneficial outcome of this mesoporous surface on osteogenic activity, it could be presumed that modulation of the macrophagic response it elicits may also contribute to initial bone-integration events. Keywords: nanotopography, inflammation, osteopontin, SPARC, stabilin 1, cytokines

Scavenging Endothelium of Pancreatic Islets Differential Expression of Stabilin-1 and Stabilin-2 in Mice and Humans

The liver sinusoidal endothelial cell hyaluronan receptor and its homolog, stabilin-1 - Their roles (known and unknown) in endocytosis.