Ibrutinib treatment 1 h prior to zymosan challenge reduces
myeloid cell recruitment over a 48 h time course.
Having shown that ibrutinib treatment reduced both neutrophil and
monocyte recruitment at 16h, we wanted to understand the full kinetics
of myeloid cell recruitment over a 48 h time period. Mice were given
ibrutinib (10 mg/kg; p.o.) 1 h prior to zymosan challenge and total
peritoneal exudate cells harvested at 2, 4, 16 and 48 h. Following
zymosan challenge there is rapid recruitment of cells into the
peritoneum within the first 4 h (Figure 2A), of which the majority are
Ly6C+Ly6G+ neutrophils (Figure 2B),
this is followed by the peak infiltration of
Ly6C+Ly6G- monocytes at 16 h (Figure
2C). Ibrutinib treatment 1 h prior to zymosan challenge significantly
reduced peak neutrophil recruitment at 2 and 4 h (Figure 2D/E). The
initial peritoneal monocyte recruitment from the blood monocytes (2 and
4 h) was unaltered in ibrutinib treated mice (Figure 2H and I) but BTK
inhibition significantly reduced the peak monocyte recruitment at 16 h
and was maintained up to 48 h (Figure J and K). Overall, the magnitude
of cellular recruitment is significantly reduced in mice given a single
ibrutinib treatment prior to zymosan challenge compared to mice given
vehicle prior to zymosan challenge over the entire 48 h time frame
studied (Figure 2 L-M).