NORMAL SERUM INCREASES ADHESION OF NEUTROPHILS TO TRACHEAL EPITHELIAL-CELLS BY A CD11B CD18-DEPENDENT MECHANISM/

Airway inflammation is characterized by intraluminal influx of inflamm atory cells, exudation of plasma, and increased procoagulant activity. We speculated that inflammatory cells might adhere to the airway surf ace epithelium in order to better localize and regulate airway inflamm atory responses. Therefore, in this study, we asked whether neutrophil s adhere to airway epithelial cells, whether serum or plasma factors i ncrease adhesion, and, if so, what the characteristics of the involved adhesion molecules are. To answer these questions, we incubated human Cr-51-labeled neutrophils from peripheral blood with dog tracheal epi thelial cells in culture in the presence or absence of normal human se rum or plasma. After 30 min, nonadhering neutrophils were centrifuged away and neutrophil adhesion was assessed by radioassay. We found that unstimulated adhesion of neutrophils to cultured epithelial cells was quite low (< 6%). However, incubation with 10% serum or plasma increa sed adhesion of neutrophils to epithelial cells dramatically (up to a mean of 71%). The serum-induced increase in adhesion was concentration dependent; even 1% serum was effective (19% adhesion). Serum adhesion factor acted selectively on epithelial surfaces, was heat sensitive, had a molecular weight > 12,000, and depended on the presence of dival ent cations. mAb 60.3 (anti-CD18) and mAb anti-Mo1 (anti-CD11b, anti-C R3) inhibited serum-induced adhesion by > 50% each. We conclude that n ormal serum and plasma contain a potent adhesion factor that induces a dhesion of neutrophils to tracheal epithelium in culture. This factor is most likely serum complement fragment iC3b. We speculate that in ai rway inflammation, exudation of plasma and local activation of complem ent system induces adhesion of neutrophils and, probably, of other pha gocytic cells to airway epithelium at the site of insult. This may con tribute to first-line airway mucosal defense.