INHIBITION OF Ca2+ INFLUX BY SURFACTANTS IN ALVEOLAR MACROPHAGES
Presenter: X. H. Sun, X.-B. Liu, J. R. Martinez, R. Castro, G. H. Zhang*
Dept. of Pediatrics, Univ. of Texas HSC, San Antonio
摘要：
An increase in cytosolic Ca2+ concentration ([Ca2+]i) is a critical signal for inflammatory mediator release in alveolar macrophages (AMs). We have demonstrated that stimulation of �-glucan receptors activates a Ca2+ influx through protein kinase C (PKC) and mitogen-activated protein kinases (MAPK) in NR8383 AMs (Sun et al, Immunopharmacology 43, 47-58, 1999). Surfactants inhibit inflammatory mediator release in lung cells. However, it is unclear whether the inhibition is through an alteration in Ca2+ signal. Therefore, the present study examined the effects of surfactants on Ca2+ influx in NR8383 AMs. [Ca2+]i was determined using the Ca2+ probe fura-2. Stimulation with 200 μg/ml zymosan induced a 117 ± 5 nM increase in [Ca2+]i in 5 min (n = 8) via �-glucan receptor-operated Ca2+ channels and this influx was significantly reduced by 1% Survanta (50 ± 6 nM, n = 5; P<0.001), 2% Exosurf (61 ± 2 nM, n = 5; P<0.001), and 0.75% Infasurf (46 ± 5 nM, n = 5; P<0.001). Activation of PKC with 20 μM 1,2-dioctanoyl-sn-glycerol induced a 61 ± 4 nM [Ca2+]i increase (n = 5) and 1% Survanta inhibited this influx by 56%. Activation of MAPK with C6-ceramide resulted in a 90 ± 4 nM [Ca2+]i increase (n = 5) and this influx was inhibited by 1% Survanta (32 ± 8 nM, n = 6; P<0.001), 2% Exosurf (40 ± 7 nM, n = 5; P<0.001), and 0.75% Infasurf (34 ± 7 nM, n = 4; P<0.002). These results suggest that surfactants inhibit Ca2+ influx in AMs probably through an interaction with downstream elements or Ca2+ channels. (Supported by NIH grant DE09270).