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J Immunol. 2012 Apr 15;188(8):4043-51. doi: 10.4049/jimmunol.1101651. Epub 2012 Mar 7.

Protein kinase C-θ is required for murine neutrophil recruitment and adhesion strengthening under flow.

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1
Department of Nephrology and Hypertensiology, Hannover Medical School, 30625 Hannover, Germany. bertram.anna@mh-hannover.de

Abstract

Protein kinase C (PKC)-θ is involved in T cell activation via regulating the avidity of the β(2) integrin LFA-1 in the immunological synapse. LFA-1 also mediates leukocyte adhesion. To investigate the role of PKC-θ in neutrophil adhesion, we performed intravital microscopy in cremaster venules of mice reconstituted with bone marrow from LysM-GFP(+) (wild-type [WT]) and PKC-θ 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-θ 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-θ in outside-in signaling following engagement of neutrophil integrins is relevant for inflammation in vivo.

PMID:
22403440
DOI:
10.4049/jimmunol.1101651
[Indexed for MEDLINE]
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