APOPTOSIS IS A MAJOR PATHWAY RESPONSIBLE FOR THE RESOLUTION OF TYPE-II PNEUMOCYTES IN ACUTE LUNG INJURY

Proliferation of type II pneumocytes has been linked to a repair proce ss during the early phase of acute lung injury, and it persists for a variable period. The mechanisms responsible for their dissolution and/ or disappearance are not known, but we speculate that it may be partly due to apoptosis. Sections of lung tissue from patients with acute lu ng injury (n = 7) and chronic interstitial pneumonia (n = 14) were sta ined for detection of apoptotic cells via specific labeling of nuclear DNA fragmentation. Results were correlated with those of proliferatin g cell nuclear antigen (PCNA) staining for cell proliferation. Marked apoptosis of CD68-negative type II pneumocytes (30 to 80%) was detecte d in four of the seven (57%) cases of acute lung injury. In these case s, representing the resolution phase of acute lung injury, PCNA positi vity in pneumocytes was extremely rare. In the 3 other cases in the ac ute/proliferation phase, apoptotic type II pneumocytes were rare where as PCNA expression was quite evident in these cells. In chronic inters titial pneumonia, only rare type II pneumocytes (<5%) exhibited apopto sis, and they showed variable staining for PCNA (up to 70%). We conclu de that proliferation of type II pneumocytes occurs during the early p hase of acute lng injury and is of variable extend and duration. In th e resolution phase of acute lung injury, extensive apoptosis of type I I pneumocytes is largely responsible for the disappearance of these ce lls. The time frame within which the apoptotic response occurs in vari able and is likely to be dependent upon the specific etiology and exte nd of the injury. In chronic interstitial pneumonia, type II pneumocyt es proliferate continuously, although to a much lesser degree than in the early phase of acute lung injury, and are minimally apoptotic.