Neutrophil migration into infected tissues is essential for host defense, but products of activated neutrophils can be quite damaging to host cells. 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 beta2 integrin-dependent adhesion in response to N-formyl-methionyl-leucyl-phenylalanine (fMLF), IL-8, or leukotriene (LT)B(4). The IC(50) for fMLF-induced migration and adhesion was 17.1 microM and 12.5 microM, 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 beta2 integrin expression. These results suggest that MARCKS, via its myristoylated aminoterminus, is a key regulator of neutrophil migration and adhesion.

Rachael E. Eckert

Laura E. Neuder

Joungjoa Park

Kenneth B. Adler

Samuel L. Jones

American Journal of Respiratory Cell and Molecular Biology

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 发表的论文报告了肺生物学领域的重要和原创性观察结果。该杂志的重点包括但不限于肺细胞和分子的细胞、生化、分子、发育、遗传和免疫学研究。

The American Journal of Respiratory Cell and Molecular Biology publishes significant and original research findings in the field of pulmonary biology. The journal focuses on various aspects including cellular, biochemical, molecular, developmental, genetic, and immunological studies of lung cells and molecules.

《American Journal of Respiratory Cell and Molecular Biology》发表肺生物学领域的重要原创研究成果。该杂志的重点包括肺细胞和分子的细胞生物学、生物化学、分子生物学、发育生物学、遗传学和免疫学研究等多个方面。

Category	Quartile
医学	2
医学, 生化与分子生物学	2
医学, 细胞生物学	2
医学, 呼吸系统	2

Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) Protein Regulation of Human Neutrophil Migration

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