Changes in Distribution and Morphology of Rat Alveolar Macrophage Subpopulations in Acute Hyperoxic Lung Injury Model

BACKGROUND: In acute lung injury, alveolar macrophages play a pivotal role in the inflammatory process during the initiation phase and in the reconstruction and fibrosis process during the later phase. Recently, it is has been proven that alveolar macrophages are constituted by morphologically, biochemically and immunologically heterogenous cell subpopulations. The possibility of alterations to these characteristics of the alveolar macrophage population during lung disease has been raised. To investigate such a possibility a hyperoxic rat lung model was made to check the distributional and morphological changes of rat alveolar macrophage subpopulation in acute hyperoxic lung injury. METHOD: Alveolar macrophage were lavaged from normal and hyperoxic lung injury rats and separated by discontinuous gradients of percoll. After cell counts of each density fraction were accessed the morphomeric analysis of alveolar macrophages was performed on cytocentrifuged preparations by transmission electron micrograph. RESULT: 1. The total alveolar macrophage cell count significantly increased up to 24 hours after hyperoxic challenge (normal control group 171.6+/-24.1x10 5 ,12 hour group 194.8+/-17.9 x10 5 , 24 hour group 207.6+/-27.1x10 5 ,p<0.05). However the 48 hour group (200.0 +/-77.8 x10 5 ) did not show a significant difference. 2. Alveolar septal thickness significantly increased up to 24 hours after hyperoxic challenge (normal control group 0.7+/-0.2mm, 12 hour group 1.5+/-0.4mm, 24 hour group 2.3 +/-0.4mm, p<0.05). However the 48 hour group did not show further change (2.5+/-0.4mm). Number of interstitial macrophage are markedly increased at 24 hour group. 3. Hypodense fraction(fraction 1 and fraction2) of alveolar macrophage showed a significant increase following hyperoxic challenge (b=0.379.b=0.694. p<0.05); however, fraction 3 was rather decreased following the hyperoxic challenge(b=-0.815. p<0.05) (,) and fraction 4 showed an irregular pattern. 4. Electron microscopic observation of alveolar macrophage from each fraction revealed considerable morphologic heterogeneity. Cells of the most dense subfraction(fraction 4) were small, round, and typically highly ruffled with small membrane pseudopods. Cells of the least dense fraction (fraction 1) were large and showed irregular eccentric nucleus and high number of heterogenous inclusions. CONCLUSION: In conclusion, these results suggest that specific hypodense alveolar macrophage subpopulation may play a an important role in the an acute hyperoxic lung injury model. But further study (,)including biochemical and immunological function of these subpopulations(,) is needed.