Quantitation of ICAM-1 expression in mouse lung during pneumonia.
In the systemic circulation, neutrophil emigration into sites of acute inflammation is mediated through the leukocyte adhesion complex, CD11/CD18. ICAM-1 is an inducible endothelial ligand for CD11a/CD18 and CD11b/CD18. Streptococcus pneumoniae elicits neutrophil emigration through a CD18-independent mechanism whereas Escherichia coli endotoxin elicits emigration through a CD18-dependent mechanism in rabbit lungs. To determine whether ICAM-1 is up-modulated in the lung during CD18-independent and CD18-dependent emigration, ultrastructural immunogold-labeling studies were performed on BALB/c mice given airway instillates of S. pneumoniae or E. coli endotoxin. Ultrathin cryosections of frozen lung tissue were immunogold labeled with the mAb YN1/1.7.4 against the murine homologue of human ICAM-1. Gold particles on the plasma membranes of alveolar endothelial and epithelial cells were quantitated by transmission electron microscopy. Capillary endothelial ICAM-1 expression did not change during neutrophil emigration toward S. pneumoniae, a CD18-independent pathway in rabbits. In contrast, ICAM-1 expression increased 4.2-fold in response to E. coli endotoxin (known to elicit CD18-dependent emigration in mice), suggesting that the mechanism of adhesion may be regulated by the expression of endothelial rather than neutrophil adhesion molecules. Constitutive expression of ICAM-1 on alveolar epithelial cells was 22-fold greater than on capillary endothelium. Epithelial expression was mainly restricted to type I pneumocytes, whereas type II pneumocytes, the precursors of type I cells, expressed little or no ICAM-1. However, during pneumonia, type II but not type I pneumocytes showed increased ICAM-1 expression, suggesting that ICAM-1 expression represents an early differentiation even in response to epithelial injury.
Burns
A R
AR
Pulmonary Research Laboratory, University of British Columbia, St. Paul's Hospital, Vancouver, Canada.
Takei
F
F
Doerschuk
C M
CM
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004727:Endothelium / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D018799:Intercellular Adhesion Molecule-1; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D011650:Pulmonary Alveoli / Q000473:pathology
D015815:Cell Adhesion Molecules; D018799:Intercellular Adhesion Molecule-1