PO administration of AMD070 increased leukocyte mobilization.

<p>Cell counts in the blood of CD-1 mice at various times after the PO administration of AMD070 at either 200 (A) or 400 (B) μg/mouse. Data shown are WBCs (●; x 10³/μL), RBCs (■; x 10⁶/μL) and platelets (▲ x 10⁶/μL) and are the means (± SEM) of 3 animals.</p

IP administration of AMD070 increased leukocyte mobilization.

<p>Cell counts in the blood of C57BL/6 mice at various times following the IP administration of AMD070 at 400 μg/mouse. A comparison of the numbers of WBCs(●; x 10³/μL), RBCs (■; x 10⁶/μL) and platelets (▲; x 10⁶/μL) are shown in panel (A) and are the means (± SEM) of 4 animals. Differential cell counts at various times are shown in panel (B) for lymphocytes (■), neutrophils (●), monocytes (▲) and eosinophils (▼) and are the means (± SEM) of 4 animals.</p

AMD070 had no effect on CCl₄ induced liver fibrosis in C57BL/6 mice.

<p>Liver fibrosis was measured using Picosirius red and scored percent areas are shown in panel (A). Panels from each of the treatment groups contain representative Picrosirius Red stained left top lobe of livers from the oil plus PBS (B), CCl₄ plus PBS (C) and CCl₄ plus AMD070 (D) groups respectively. Bars represent 1 mm for the top image and 50 μm for the lower images in each panel.</p

Leukocyte mobilization induced by AMD070 was the result of increase in lymphocytes.

<p>Differential cell counts in the blood of CD-1 mice at various times following PO administration of AMD070 at either 200 (A) or 400 (B) μg/mouse. Data are shown for lymphocytes (■), neutrophils (●), monocytes (▲) and eosinophils (▼) and are the means (± SEM) of 3 animals.</p

AMD070 did not alleviate BLM induced lung inflammation at end point as demonstrated by H & E stained lungs.

<p>Graph in (A) represents the means (± SEM) of percent surface area with high inflammatory cell infiltrate, as measured by H&E staining intensity. Representative H & E stained lungs of PBS plus acetate buffer (B), BLM plus acetate buffer (C) and BLM plus AMD070 (D) treated mice. Black arrows indicate areas with increased inflammatory cell infiltrate. AB indicates acetate buffer and this notation is used for the following Figs.</p

Pharmacokinetics of AMD070 in the lung of CD-1 mice.

<p>Concentration of AMD070 in the lungs of CD-1 mice at various times after PO administration at 400 μg/animal. Data represent the means (± SEM) of 3 mice. Horizontal dash line represents EC₉₀ of 44ng/mL. (SEM, Standard error of mean).</p

AMD070 had neither an effect on the <i>Acta2</i> and <i>Col1a1</i> transcription levels in the liver nor serum AST levels.

<p>The relative transcription levels of <i>Acta2</i> and <i>Col1a1</i> are shown relative to housekeeping genes <i>Gapdh</i> (A) and <i>Tbp</i> (B). Serum AST levels are shown in panel (C). Prebleed is serum collected prior to CCl₄ and AMD070 treatment. Treated is serum collected one day after the last AMD070 or PBS treatment.</p

AMD070 did not alleviate BLM induced lung fibrosis as demonstrated by Masson’s Trichrome stained lungs.

<p>Graph in (A) represents the means (± SEM) of percent lung fibrosis. Representative Masson’s Trichrome stained lungs of PBS plus acetate buffer (B), BLM plus acetate buffer (C) and BLM plus AMD070 (D) treated mice. Note the intense cyan staining in the middle and lower panels indicative of collagen deposition in the lung parenchyma of BLM-treated mice. Bars represent 200 μm for the middle and 20 μM for the lower panel.</p

AMD070 alleviated BLM induced mortality.

<p>Kaplan Meier plot of animals in the PBS plus acetate buffer, BLM plus acetate buffer and BLM plus AMD070 groups.</p

Phoenix WinNonlin Noncompartmental analysis of AMD070 concentration in the plasma, lung and liver of C57BL/6 mice following IP or SC administration of AMD070 at 400 μg/mouse.

<p>Values for Cmax are provided as μg/mL for plasma and as μg/g for liver and lung. Values for AUC are provided as μg/mL for plasma and as μg/g for lung and liver.</p