Am. J. Respir. Cell Mol. Biol., Vol 10, No. 1, 01 1994, 65-71.
Interferon-gamma increases cytoplasmic motility of alveolar macrophages via nitric oxide-dependent signaling pathways
T Fukushima, K Sekizawa, Y Jin and H Sasaki
Department of Geriatric Medicine, Tohoku University School of Medicine, Sendai, Japan.
The effects of interferon-gamma (IFN-gamma) were investigated on
cytoplasmic motility of alveolar macrophages (AM) from rat lungs in vitro.
Cytoplasmic motility was examined by measuring remnant field strength from
the cell surface of AM containing Fe3O4 particles, and the relaxation rate
(lambda 0; min-1), which is related to cytoplasmic motility, was
determined. IFN-gamma caused an increase in lambda 0 in a
concentration-dependent fashion with the maximal effect at 1,000 U.
Dibutyryl cyclic GMP (db cyclic GMP; 10(-3) M) mimicked IFN-gamma- induced
effects, but db cyclic AMP (10(-3) M) decreased lambda 0. IFN- gamma (1,000
U)-induced increases in lambda 0 were concentration- dependently inhibited
by NG-monomethyl-L-arginine (L-NMMA) with complete inhibition of a
concentration of 10(-4) M and were also completely inhibited by either
methylene blue (10(-5) M) or KT 5823 (10(-5) M), a specific inhibitor of
protein kinase G. IFN-gamma (1,000 U) caused significant nitrite (NO2-)
production from the control values of 0.2 +/- 0.1 to 10.0 +/- 0.2 microM/24
h per 10(6) cells (P < 0.001, n = 10), and this increase in NO2-
production by IFN-gamma (1,000 U) was completely inhibited by L-NMMA
(10(-4) M). IFN-gamma caused a concentration-dependent increase in a
filamentous-actin (F-actin) content with the maximal effect at 1,000 U. db
cyclic GMP (10(-3) M) mimicked IFN-gamma induced effects on F-actin
formation.(ABSTRACT TRUNCATED AT 250 WORDS)
