Multiple BTK inhibitors reduce myeloid cell recruitment to the peritoneum and reduce recruitment to the blood from the spleen.
Having shown that ibrutinib, the first BTK inhibitor to gain FDA approval, inhibits neutrophil and monocyte recruitment to the peritoneum, we wanted to test a range of both more selective (Acalabrutinib) and less potent or more/less selective commercially available BTK inhibitors. All BTK inhibitors tested reduced cellularity in the peritoneum 16 h after zymosan challenge (Figure 3A). This was largely due to reductions in neutrophil accumulation (Figure 3B), while there was a similar trend in reducing monocyte accumulation (Figure 3C). We also measured myeloid cell numbers in the blood. Following zymosan challenge neutrophils and monocytes are mobilised to the blood from bone marrow or splenic reserves (Figure 3D). Overwhelmingly, mice treated with a BTK inhibitor prior to zymosan challenge had fewer neutrophils (Figure 3E) and monocytes (Figure 3F) in the blood at 16 h, the exception being Acalabrutinib pre-treatment which did not significantly alter neutrophil or monocyte mobilisation to the blood. These results collectively point to a central role in BTK in the regulation of neutrophil and monocyte recruitment in vivo .