| First Author | Xu Z | Year | 2015 |
| Journal | Blood | Volume | 126 |
| Issue | 3 | Pages | 373-7 |
| PubMed ID | 26056166 | Mgi Jnum | J:226365 |
| Mgi Id | MGI:5697134 | Doi | 10.1182/blood-2015-03-636720 |
| Citation | Xu Z, et al. (2015) Interaction of kindlin-3 and beta2-integrins differentially regulates neutrophil recruitment and NET release in mice. Blood 126(3):373-7 |
| abstractText | Kindlin-3 essentially supports integrin activation in blood cells. Absence of kindlin-3 in humans causes leukocyte adhesion deficiency-III characterized with severe bleeding disorder and recurrent infections. Previously, we generated kindlin-3 knock-in (K3KI) mice carrying an integrin-interaction disrupting mutation in kindlin-3 and verified the functional significance of the binding of kindlin-3 to integrin alphaIIbbeta3 in platelets. Here, using K3KI mice, we functionally evaluate the crosstalk between kindlin-3 and beta2-integrins in neutrophils. Although the kindlin-3 mutant in K3KI neutrophils is normally expressed, its binding ability to beta2-integrins in neutrophils is disabled. In vitro and in vivo analyses disclose that beta2-integrin-mediated K3KI neutrophil adhesion and recruitment are significantly suppressed. Interestingly, the ability of releasing neutrophil extracellular traps (NETs) from K3KI neutrophils is also compromised. Substantially, a peptide derived from the integrin beta2 cytoplasmic tail that can inhibit the interaction between kindlin-3 and beta2-inegrins significantly jeopardizes NET release without affecting neutrophil adhesion and recruitment under the experimental conditions. These findings suggest that crosstalk between kindlin-3 and beta2-integrins in neutrophils is required for supporting both neutrophil recruitment and NET release, but the involved regulatory mechanisms in these two cellular events might be differential, thus providing a novel therapeutic concept to treat innate immune-related diseases. |
