Slauson D O, Lay J C, Castleman W L, Neilsen N R
Department of Pathology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853.
Inflammation. 1989 Aug;13(4):429-41. doi: 10.1007/BF00914926.
The pulmonary alveolar macrophage (PAM) is central to lung cellular defenses and is a potential participant in lung injury, but little is known about the influence of the nature and anatomic pattern of acute lung injury on PAM function. To assess the relationship between ongoing pulmonary inflammation and PAM function, we evaluated PAM phagocytic kinetics in a model system of experimental interstitial adjuvant pneumonitis (EIAP) in calves. PAMs were obtained from lung one and seven days postinduction (dpi) of EIAP. Lesions were typical of EIAP, characterized by acute multifocal to coalescing exudative interstitial pneumonitis at 1 dpi, which progressed to granulomatous interstitial pneumonitis by 7 dpi. The total recoverable lung cells and percentage of neutrophils (PMNs) were elevated (P less than 0.01) from animals with EIAP at both 1 and 7 dpi, and there was a four-fold increase (P less than 0.01) in the PAM yield by 7 dpi. Linear regression equations revealed that a larger proportion of control PAMs were phagocytic than were PAMs from animals with EIAP. The mean initial phagocytic rates of PAM following acute lung injury were significantly elevated (P less than 0.05) over controls; this difference was concentration dependent and required a phagocytic bead stimulus concentration in excess of 12.5 x 10(6) beads/ml. PAMs from animals with EIAP had a greater maximum rate of phagocytosis (Vmax) and Km than control PAMs. PAMs from animals with EIAP had a slightly higher proportion of cells which phagocytosed multiple beads. Levels of beta-glucuronidase were elevated (P less than 0.02) in PAM from animals with EIAP at 7 dpi. The results document enhanced PAM phagocytic function in EIAP and differ from our previous experiments in which depressed PAM phagocytic indices were obtained in a model of virus-induced acute bronchiolitis and alveolitis. The functional activities of the PAMs thus appear to be modified by injury-specific events in the lung microenvironment which may, in part, reflect the nature and anatomic pattern of developing pulmonary inflammatory reactions.
肺泡巨噬细胞（PAM）是肺部细胞防御的核心，也是肺损伤的潜在参与者，但关于急性肺损伤的性质和解剖模式对PAM功能的影响却知之甚少。为了评估持续的肺部炎症与PAM功能之间的关系，我们在犊牛实验性间质性佐剂肺炎（EIAP）模型系统中评估了PAM的吞噬动力学。PAM取自EIAP诱导后1天和7天的肺组织。病变为EIAP的典型表现，1 dpi时为急性多灶性至融合性渗出性间质性肺炎，到7 dpi时发展为肉芽肿性间质性肺炎。EIAP动物在1 dpi和7 dpi时，可回收的肺细胞总数和中性粒细胞（PMN）百分比均升高（P < 0.01），到7 dpi时PAM产量增加了四倍（P < 0.01）。线性回归方程显示，与EIAP动物的PAM相比，对照PAM中具有吞噬作用的比例更大。急性肺损伤后PAM的平均初始吞噬率显著高于对照组（P < 0.05）；这种差异呈浓度依赖性，且需要吞噬珠刺激浓度超过12.5×10⁶个珠子/毫升。EIAP动物的PAM比对照PAM具有更高的最大吞噬率（Vmax）和米氏常数（Km）。EIAP动物的PAM中吞噬多个珠子的细胞比例略高。7 dpi时，EIAP动物的PAM中β-葡萄糖醛酸酶水平升高（P < 0.02）。结果表明EIAP中PAM的吞噬功能增强，这与我们之前的实验不同，在之前的病毒诱导急性细支气管炎和肺泡炎模型中获得的是PAM吞噬指数降低。因此，PAM的功能活性似乎受到肺微环境中损伤特异性事件的影响，这可能部分反映了正在发展的肺部炎症反应的性质和解剖模式。
