Details

Autor(en) / Beteiligte

• Hu, Maowen
• Lin, Xinchun
• Du, Qiaoting
• Miller, Edmund J
• Wang, Ping
• Simms, H. Hank

Titel

Regulation of polymorphonuclear leukocyte apoptosis: role of lung endothelium-epithelium bilayer transmigration

Ist Teil von

• American journal of physiology. Lung cellular and molecular physiology, 2005-02, Vol.288 (2), p.L266-L274

Ort / Verlag

United States

Erscheinungsjahr

2005

Quelle

MEDLINE

Beschreibungen/Notizen

• Division of Surgical Research, Department of Surgery, North Shore University Hospital and Long Island Jewish Medical Center, Manhasset, New York Submitted 4 June 2004 ; accepted in final form 27 September 2004 Delayed polymorphonuclear leukocyte (PMN) apoptosis exacerbates acute lung injury. To reach the alveolar spaces, PMNs must migrate across both pulmonary endothelial and epithelial cell layers. We hypothesized that transmigration across the endothelium-epithelium bilayer suppresses PMN apoptosis and sought to elucidate the underlying mechanisms. PMNs freshly isolated from normal volunteers were allowed to migrate across polycarbonate membranes alone or membranes coated with a bilayer of human lung endothelial and epithelial cells. After migration toward different chemoattractants (IL-8, formyl-Met-Leu-Phe, or leukotriene B 4 ), PMN apoptosis and caspase activities were assessed by annexin V, histology, and enzymatic assays, respectively. Messenger RNA and specific protein expression in three receptor ligand-mediated, apoptosis-inducing pathways (Fas, TNF- , and TNF-related apoptosis-inducing ligand) were further examined by gene array, RT-PCR, flow cytometry, and Western blot analyses. The data demonstrated that transbilayer migration suppressed PMN apoptosis, and this effect was not chemoattractant type specific. Kinetic analyses further showed that the delay of apoptosis was sustained to at least 18 h. Transbilayer migration caused significant decreases in caspase (-3, -8, and -9) activities. The changes in apoptosis-related gene expression support the survival role of transbilayer migration. Furthermore, the reduced apoptosis was correlated with downregulation of Fas ligand and TNF receptor 1 expression. Our data reveal that migration across a lung endothelium-epithelium bilayer suppresses PMN apoptosis. The decreased activity and/or expression of proapoptotic proteins may provide possible targets for the regulation of inappropriate delay in PMN apoptosis during lung inflammation and injury. neutrophils; chemotaxis; interleukin-8 Address for reprint requests and other correspondence: M. Hu, Dept. of Surgery, North Shore Univ. Hospital and Long Island Jewish Medical Center, 350 Community Dr., Manhasset, NY 11030 (E-mail: mhu{at}nshs.edu )