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Abnormal Migration Phenotype of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2^-/- Neutrophils in Zigmond Chambers Containing Formyl-Methionyl-Leucyl-Phenylalanine Gradients¹

Michael O. Hannigan^*, Lijun Zhan^*, Youxi Ai^*, Alexey Kotlyarov, Matthias Gaestel and Chi-Kuang Huang^2,*

^* Department of Pathology, University of Connecticut Health Center, Farmington, CT 06030; and Center for Biochemistry/Institute of Biochemistry, Medical School of Hannover, Hanover, Germany.

Time-lapsed video microscopy and confocal imaging were used to study the migration of wild-type (WT) and mitogen-activated protein kinase-activated protein kinase 2 (MK2)^-/- mouse neutrophils in Zigmond chambers containing fMLP gradients. Confocal images of polarized WT neutrophils showed an intracellular gradient of phospho-MK2 from the anterior to the posterior region of the neutrophils. Compared with WT neutrophils, MK2^-/- neutrophils showed a partial loss of directionality but higher migration speed. Immunoblotting experiments showed a lower protein level of p38 mitogen-activated protein kinase and a loss of fMLP-induced extracellular signal-related kinase phosphorylation in MK2^-/- neutrophils. These results suggest that MK2 plays an important role in the regulation of neutrophil migration and may also affect other signaling molecules.

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