Analysis of PD-1 expression in the monocyte subsets from non-septic and septic preterm neonates

Programmed death-1 (PD-1) receptor system represents a part of recently reported immunoregulatory pathway. PD-1 is an immune checkpoint molecule, which plays an important role in downregulating the immune system proinflammatory activity. Until recently, PD-1 expression was not established on immune cells of the preterm infants. The study objectives were to confirm expression of the PD-1 receptors on the monocytes isolated from very low birth weight newborns (VLBW), and to analyze their expression during the first week of life and late-onset sepsis. Peripheral blood mononuclear cells were isolated from 76 VLBW patients without early-onset sepsis on their 5th day of life (DOL). PD-1 expression was determined on the monocyte subsets (classical, intermediate, non-classical) by flow cytometry. In case of late-onset sepsis (LOS), the same analysis was performed. Our results demonstrated that on the 5th DOL, PD-1 receptors were present in all the monocyte subsets. Children, whose mothers had received antenatal steroids, presented higher absolute numbers of non-classical monocytes with PD-1 expression. Infants born extremely preterm who later developed LOS, initially showed a lower percentage of PD-1 receptor-positive intermediate monocytes in comparison to neonates born very preterm. During LOS, we observed a rise in the percentage of classical monocytes with PD-1 expression. In case of septic shock or fatal outcome, there was a higher percentage and absolute count of intermediate monocytes with PD-1 expression in comparison to children without these complications. In conclusion, monocytes from VLBW children express PD-1 receptors. Antenatal steroid administration seems to induce PD-1 receptor expression in the non-classical monocytes. PD-1 might play a role in immunosuppressive phase of sepsis in the prematurely born children with septic shock and fatal outcome

Synthesis and in vitro antiproliferative activity of novel (4-chloro- and 4-acyloxy-2-butynyl)thioquinolines

The series of new acetylenic thioquinolines containing propargyl, 4-chloro-2-butynyl, and 4-acyloxy-2-butynyl groups have been prepared and tested for antiproliferative activity in vitro against human [SW707 (colorectal adenocarcinoma), CCRF/CEM (leukemia), T47D (breast cancer)] and murine [P388 (leukemia), B16 (melanoma)] cancer lines. Most of the obtained compounds exhibited antiproliferative activity, especially compounds 8, 12, and 21 showed the ID50 values ranging from 0.4 to 3.8 μg/ml comparable to that of cisplatin used as reference compounds

Analysis of the monocyte subpopulations in the patients with or without septic shock.

<p>(A) Absolute numbers of monocyte subsets. (B) Percentages of PD-1 positive cells. (C) Absolute numbers of PD-1 positive cells. Data presented as median and IQR (box), compared with Wilcoxon test. Whiskers—range within 1.5 IQR. Classical monocytes are presented as a black graph, intermediate monocytes are presented as a graph with horizontal lines, whereas non-classical monocytes are presented as a graph with vertical lines. P-value was significant in case of *p<0.05.</p

Counts of monocyte subsets, monocyte subsets with PD-1 expression, and a percentage of PD-1⁺ cells within each monocyte subset in the blood samples from VLBW infants collected on the 5^th DOL.

<p>Data presented as median and IQR.</p

Comparison of selected demographic variables and hospitalization data of the patients in the two studied groups.

<p>Comparison of selected demographic variables and hospitalization data of the patients in the two studied groups.</p

Monocyte populations and PD-1 expression in the before-LOS group of VLBW infants.

<p>Patients were subdivided into groups based on the level of their gestational age at birth. (A) Absolute numbers of monocyte subsets. (B) Percentages of PD-1 expressing monocytes. (C) Absolute numbers of PD-1 expressing monocytes. Data presented as median and IQR (box), compared with Wilcoxon test. Whiskers—range within 1.5 IQR. Classical monocytes are presented as a black graph, intermediate monocytes are presented as a graph with horizontal lines, whereas non-classical monocytes are presented as a graph with vertical lines. P-value was significant in case of *p<0.05.</p

Analysis of the monocyte subpopulations in VLBW infants who either did nor did not survived LOS.

<p>(A) Absolute numbers of monocyte subsets. (B) Percentages of PD-1-positive cells. (C) Absolute numbers of PD-1 positive cells. Data presented as median and IQR (box), compared with Wilcoxon test. Whiskers—range within 1.5 IQR. Classical monocytes are presented as a black graph, intermediate monocytes are presented as a graph with horizontal lines, whereas non-classical monocytes are presented as a graph with vertical lines. P-value was significant in case of *p<0.05.</p