PNEUMOCYSTIS CARNII INDUCES ICAM-1 EXPRESSION IN LUNG EPITHELIAL-CELLS THROUGH A TNF-ALPHA-MEDIATED MECHANISM

Inflammatory cell recruitment contributes to respiratory impairment du ring Pneumocystis carinii pneumoma. We evaluated expression of interce llular adhesion molecule-1 (ICAM-1), a key participant in leukocyte ac cumulation, in rats with P. carinii pneumonia. Immunostaining for ICAM -1 was most marked on bronchiolar epithelium but was also evident on t ype II pneumocytes, endothelium, and macrophages. Lung from normal and dexamethasone-treated uninfected animals exhibited markedly less ICAM -1. We hypothesized that P. carinii promoted ICAM-1 expression in epit helium through tumor necrosis factor-alpha (TNF-alpha) release from ma crophages or that P. carinii directly stimulated ICAM-1 expression. Al veolar macrophages were incubated with P. carinii, and the medium was added to A549 epithelial cells. Treatment of macrophages with P. carin ii enhanced A549 ICAM-1, which was inhibited with antibody to TNF-alph a. To determine whether P. carinii alone also stimulated ICAM-1, A549 cells were cultured with P. carinii, also augmenting ICAM-1. Of note, A549 ICAM-1 expression from P. carinii alone was less than with P. car inii-exposed macrophages. Thus ICAM-1 is enhanced in lung epithelium d uring P. carinii infection, in part, through TNF-alpha-mediated mechan isms.