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Neutrophil influx into the lung and airways and resultant inflammation characterizes diseases such as chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis. To migrate, neutrophils must reorganize the actin cytoskeleton to establish a leading edge pseudopod and a trailing edge uropod. The actin-binding protein myristoylated alanine-rich C-kinase substrate (MARCKS) has been shown to bind and cross-link actin in a variety of cell types and to co-localize with F-actin in the leading edge lamellipodium of migrating fibroblasts. The hypothesis that MARCKS has a role in the regulation of neutrophil migration was tested using a cell-permeant peptide derived from the MARCKS myristoylated aminoterminus (MANS peptide). Treatment of isolated human neutrophils with MANS significantly inhibited both their migration and \u03b22 integrin-dependent adhesion in response to N-formyl-methionyl-leucyl-phenylalanine (fMLF), IL-8, or leukotriene (LT)B4. The IC50 for fMLF-induced migration and adhesion was 17.1 \u03bcM and 12.5 \u03bcM, respectively. MANS significantly reduced the F-actin content in neutrophils 30 seconds after fMLF stimulation, although the peptide did not alter the ability of cells to polarize or spread. MANS did not alter fMLF-induced increases in surface \u03b22 integrin expression. These results suggest that MARCKS, via its myristoylated aminoterminus, is a key regulator of neutrophil migration and adhesion.<\/jats:p>","DOI":"10.1165\/rcmb.2008-0394oc","type":"journal-article","created":{"date-parts":[[2009,7,2]],"date-time":"2009-07-02T22:37:46Z","timestamp":1246574266000},"page":"586-594","source":"Crossref","is-referenced-by-count":64,"title":["Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) Protein Regulation of Human Neutrophil Migration"],"prefix":"10.1093","volume":"42","author":[{"given":"Rachael E.","family":"Eckert","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E.","family":"Neuder","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joungjoa","family":"Park","sequence":"additional","affiliation":[{"name":"Center for Comparative Medicine and Translational 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