Snipes M B, Harkema J R, Hotchkiss J A, Bice D E
Inhalation Toxicology Research Institute, Albuquerque, New Mexico 87185, USA.
Exp Lung Res. 1997 Jan-Feb;23(1):65-84. doi: 10.3109/01902149709046048.
This study evaluated polymorphonuclear leukocyte (PMN) involvement in translocation of dust to bronchial lymph nodes after deposition of dust in the lungs of control and neutropenic F344/N rats. Rats were rendered neutropenic with an intraperitoneal (IP) injection of anti-rat PMN antiserum (APA); control rats were injected IP with 0.9% saline solution. Eighteen hours after IP injections, control and APA-treated rats were instilled intratracheally with 5 x 10(8) microspheres suspended in 0.9% saline solution, which caused an influx of PMNs into the pulmonary airspaces of control rats, but not of APA-treated rats. One day postinstillation (PI), 77.2% of the microspheres recovered in bronchoalveolar lavage fluid (BALF) from control rats were associated with pulmonary alveolar macrophages (PAMs) and 18.8% with PMNs; 4.0% were free. In BALF from the APA-treated rats, 66.3% of the microspheres were associated with PAMs and 0.3% with PMNs; 36.3% were free. Two days PI, about 95% of the microspheres in BALF from control and APA-treated rats were associated with PAMs; by 4 and 7 days PI, essentially 100% were with PAMs. Amounts of microspheres translocated to bronchial lymph nodes of control rats were four fold less than in the APA-treated rats on days 2, 4, and 7 PI (p < .05). The results suggest that PMNs in pulmonary airspaces of F344/N rats phagocytize dust and thereby interfere with the mechanism(s) involved in dust penetration into the pulmonary interstitium.
本研究评估了在对照和中性粒细胞减少的F344/N大鼠肺部沉积粉尘后,多形核白细胞(PMN)在粉尘向支气管淋巴结转运过程中的作用。通过腹腔注射抗大鼠PMN抗血清(APA)使大鼠中性粒细胞减少;对照大鼠腹腔注射0.9%盐溶液。腹腔注射18小时后,给对照大鼠和经APA处理的大鼠气管内滴注悬浮于0.9%盐溶液中的5×10⁸个微球,这导致微球流入对照大鼠的肺腔,但未流入经APA处理的大鼠肺腔。滴注后1天(PI),对照大鼠支气管肺泡灌洗液(BALF)中回收的微球,77.2%与肺泡巨噬细胞(PAM)相关,18.8%与PMN相关;4.0%为游离状态。在经APA处理的大鼠的BALF中,66.3%的微球与PAM相关,0.3%与PMN相关;36.3%为游离状态。滴注后2天,对照大鼠和经APA处理的大鼠BALF中约95%的微球与PAM相关;到滴注后4天和7天,基本上100%的微球与PAM相关。在滴注后第2天、第4天和第7天,转运至对照大鼠支气管淋巴结的微球数量比经APA处理的大鼠少四倍(p<0.05)。结果表明,F344/N大鼠肺腔中的PMN吞噬粉尘,从而干扰了粉尘进入肺间质所涉及的机制。