| First Author | Bertram A | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 8 | Pages | 4043-51 |
| PubMed ID | 22403440 | Mgi Jnum | J:184084 |
| Mgi Id | MGI:5320238 | Doi | 10.4049/jimmunol.1101651 |
| Citation | Bertram A, et al. (2012) Protein kinase C-theta is required for murine neutrophil recruitment and adhesion strengthening under flow. J Immunol 188(8):4043-51 |
| abstractText | Protein kinase C (PKC)-theta is involved in T cell activation via regulating the avidity of the beta(2) integrin LFA-1 in the immunological synapse. LFA-1 also mediates leukocyte adhesion. To investigate the role of PKC-theta in neutrophil adhesion, we performed intravital microscopy in cremaster venules of mice reconstituted with bone marrow from LysM-GFP(+) (wild-type [WT]) and PKC-theta gene-deficient (Prkcq(-/-)) mice. Following stimulation with CXCL1, both WT and Prkcq(-/-) cells became adherent. Although most WT neutrophils remained adherent for at least 180 s, 50% of Prkcq(-/-) neutrophils were detached after 105 s and most by 180 s. Upon CXCL1 injection, rolling of all WT neutrophils stopped for 90 s, but rolling of Prkcq(-/-) neutrophils started 30 s after CXCL1 stimulation. A similar neutrophil adhesion defect was seen in vitro, and spreading of Prkcq(-/-) neutrophils was delayed. Prkcq(-/-) neutrophil recruitment was impaired in fMLP-induced transmigration into the cremaster muscle, thioglycollate-induced peritonitis, and LPS-induced lung injury. We conclude that PKC-theta mediates integrin-dependent neutrophil functions and is required to sustain neutrophil adhesion in postcapillary venules in vivo. These findings suggest that the role of PKC-theta in outside-in signaling following engagement of neutrophil integrins is relevant for inflammation in vivo. |
