aureus (Fig. 2A) or S. typhimurium (Fig. 2B) resulted in markedly increased PMN accumulation in the peritoneal cavity at 12 and 24 h post septic challenge. By contrast, infant mice in response to bacterial infection recruited significantly fewer PMNs into the peritoneal cavity than adult mice (p < 0.05), albeit the population of peritoneal macrophages Obeticholic Acid ic50 was identical between infant and adult
mice (Fig. 2A and B). To examine whether the reduced PMN recruitment observed in infant mice after septic challenge is due to a diminished number of circulating PMNs, we assessed systemic granulocytes and monocytes in infant and adult mice before and after bacterial infection. The percentage of granulocytes (Gr-1+CD11b+ cells) (Fig. 2C) and monocytes (F4/80+CD11b+ cells) (Fig. 2D) in the circulation of infant and adult mice increased substantially in response to either S. aureus or S. typhimurium challenge; however, there were no significant differences in circulating granulocytes and monocytes seen between infant and adult mice (Fig. 2C and D). We further assessed the percentage of monocytes
(Gr-1+ CD11b+F4/80+ cells) and immature cells (Gr-1+CD11b+CD31+ selleck chemical cells) in the circulating granulocyte population. Both Gr-1+CD11b+F4/80+ cells (Fig. 2E) and Gr-1+CD11b+CD31+ cells (Fig. 2F) had slightly increases post septic challenge, but they were comparable between infant and adult mice (Fig. 2E and F). The chemokine receptor CXCR2 is essential for the recruitment of PMNs, and reduced CXCR2 expression correlates closely with an inability of PMNs to migrate from the circulation into the infectious site during microbial sepsis [28, 29]. Therefore, we assessed surface expression of CXCR2 on circulating PMNs in infant and adult mice before and after bacterial infection. Circulating infant PMNs exhibited less constitutive expression of CXCR2 than circulating adult PMNs (p < 0.05) (Fig. 3A and B). S. aureus or S. typhimurium challenge downregulated CXCR2 expression on circulating adult
PMNs, and caused further reduction of CXCR2 in circulating infant PMNs (p < 0.05 versus adult PMNs) (Fig. 3A and B). Consistent with the diminished CXCR2 expression, infant PMNs showed considerable 3-mercaptopyruvate sulfurtransferase less chemotaxis toward the chemoattractant CXCL2 than adult PMNs in the presence or absence of bacterial challenges (p < 0.05) (Fig. 3C). G protein-coupled receptor kinase 2 (GRK2), a serine-threonine kinase, participates in phosphorylation and internalization of chemokine receptors and thus downregulates the expression of chemokine receptors including CXCR2 [30-32]. It is possible that infant PMNs may express more GRK2, which in turn leads to the downregulation of CXCR2. However, there were no significant differences in constitutive and bacteria-stimulated GRK2 expression found between infant and adult PMNs (Fig. 3D and E).
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