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 CD11 a/CD18 and C D11b/CD18. Streptococcus pneumoniae elicits neutrophil emigration thro ugh a CD18-independent mechanism whereas Escherichia coli endotoxin el icits emigration through a CD18-dependent mechanism in rabbit lungs. T o determine whether ICAM-1 is up-modulated in the lung during CD18-ind ependent and CD18-dependent emigration, ultrastructural immunogold-lab eling studies were performed on BALB/c mice given airway instillates o f S. pneumoniae or E. coli endotoxin. Ultrathin cryosections of frozen lung tissue were immunogold labeled with the mAb YN1/ 1.7.4 against t he murine homologue of human ICAM-1. Cold particles on the plasma memb ranes of alveolar endothelial and epithelial cells were quantitated by transmission electron microscopy. Capillary endothelial ICAM-1 expres sion 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 a dhesion may be regulated by the expression of endothelial rather than neutrophil adhesion molecules. Constitutive expression of ICAM-1 on al veolar epithelial cells was 22-fold greater than on capillary endothel ium. Epithelial expression was mainly restricted to type I pneumocytes , whereas type II pneumocytes, the precursors of type I cells, express ed little or no ICAM-1. However, during pneumonia, type II but not typ e I pneumocytes showed increased ICAM-1 expression, suggesting that IC AM-1 expression represents an early differentiation event in response to epithelial injury.