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INDUCIBLE NITRIC OXIDE SYNTHASE (INOS) IN MURINE PULMONARY MICROVASCULAR ENDOTHELIAL CELLS (PMEC), BUT NOT NEUTROPHILS, STIMULATES NEUTROPHIL APOPTOSIS.
Author(s) -
wang lefeng,
farley Kalamo,
Mccormack David,
Mehta Sanjay
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a750-d
Subject(s) - nitric oxide synthase , apoptosis , chemistry , nitric oxide , necrosis , microbiology and biotechnology , immunology , pharmacology , medicine , biology , biochemistry , organic chemistry
Neutrophils (PMN) migrating into the lung demonstrate delayed apoptosis. As nitric oxide (NO) regulates many aspects of PMN function, eg. adhesion, migration, we investigated the effects of iNOS on PMN caspase‐3 activity (C3A), a key enzyme in the apoptosis cascade. PMEC and bone marrow PMN were isolated from iNOS+/+ and iNOS−/− mice. PMN were cultured alone or co‐cultured with PMEC monolayers with or without LPS/IFN‐γ. At different time points, PMN or trans‐PMEC migrated PMN were collected and their C3A was measured. In unstimulated PMN, C3A increased 8.5±1.3‐fold at 4 and 8 hr, and declined at 22 hr. LPS/IFN‐γ decreased peak C3A by 40–50% vs unstimulated PMN. In trans‐PMEC migrated PMN, the increase in C3A was delayed to 22 hr. Moreover, C3A was significantly greater in PMN following migration through iNOS+/+ PMEC vs through iNOS−/− PMEC, although the migration rate was similar at all time points. Under all conditions, changes in C3A and time course were identical between iNOS−/− and iNOS+/+ PMN. These data suggests that iNOS expressed in PMEC, but not in PMN, has an important pro‐apoptotic effect on trans‐PMEC migrated PMN. Caspase‐3 activity (p mol/10 5 cells · hr) of PMN (n=4‐5) Treatment 0 hr 4 hr 8 hr 22 hr iNOS+/+ PMN