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F. Denorme et al.
GPIba binding site in the VWF A1 domain.22 Indeed, anti- VWF A1 nanobody treatment resulted in a similar reduc- tion of leukocyte recruitment as that present in VWF-defi- cient animals (Online Supplementary Table S1). This nanobody was previously shown to reduce overall leuko-
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cyte recruitment in a model of immune complex-mediat- ed vasculitis and a model of irritant contact dermatitis, suggesting that the pro-inflammatory properties of the VWF A1 domain can play an important role in several set- tings.22 Pendu et al. previously demonstrated that VWF,
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Figure 5. The von Willebrand factor A1 domain recruits monocytes, neutrophils and T- cells to the brain after acute ischemic stroke. Transient focal cerebral ischemia was induced by occluding the right middle cerebral artery for 60 min, followed by 23 h of reper- fusion. Immediately at the start of reperfusion, mice were intra- venously treated with 10 mg/kg of either control (KB- VWF-004 bv) or inhibitory anti- VWF A1 nanobody (KB-VWF- 006 bv). Twenty-four hours after the transient arterial occlusion, recruitment of spe- cific subsets of white blood cells (WBC) to each hemi- sphere was determined by flow cytometry. (A) WBC (CD45high). (B) Myeloid WBC (CD45high; CD11b+). (C) Lymphoid WBC (CD45high; CD11b-; CD11c-). (D) Inflammatory monocytes (CD45high; CD11b+; Ly6C+; Ly6G- ). (E) Neutrophils (CD45high; CD11b+; Ly6G+). (F) T cells (CD45high; CD11b-; CD11c-; CD3e+). (G) CD3neg lymphocytes (CD45high; CD11b-; CD11c-; CD3e-). *P<0.05; **P<0.01; ***P<0.005; ****P<0.001 (n=10-11). Ipsi: ipsilateral cerebral hemisphere; contra: contralateral cerebral hemi- sphere.
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haematologica | 2021; 106(3)