Pneumocystis carinii induces ICAM-1 expression in lung epithelial cells through a TNF-alpha-mediated mechanism.
Inflammatory cell recruitment contributes to respiratory impairment during Pneumocystis carinii pneumonia. We evaluated expression of intercellular adhesion molecule-1 (ICAM-1), a key participant in leukocyte accumulation, in rats with P. carinii pneumonia. Immunostaining for ICAM-1 was most marked on bronchiolar epithelium but was also evident on type 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 epithelium through tumor necrosis factor-alpha (TNF-alpha) release from macrophages or that P. carinii directly stimulated ICAM-1 expression. Alveolar macrophages were incubated with P. carinii, and the medium was added to A549 epithelial cells. Treatment of macrophages with P. carinii enhanced A549 ICAM-1, which was inhibited with antibody to TNF-alpha. 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. carinii-exposed macrophages. Thus ICAM-1 is enhanced in lung epithelium during P. carinii infection, in part, through TNF-alpha-mediated mechanisms.
Yu
M L
ML
Department of Pulmonary, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Limper
A H
AH
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D008168:Lung / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D008175:Lung Neoplasms; D016676:Macrophages, Alveolar / Q000276:immunology*; D011010:Pneumocystis / Q000502:physiology*; D011020:Pneumonia, Pneumocystis / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology*
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone