Mechanisms of serum-enhanced adhesion of human alveolar macrophages to epithelial cells.

Adhesive interactions between macrophages and epithelial cells in the pulmonary alveoli may be important in the pathogenesis of inflammatory lung diseases, such as those induced by cigarette smoking. Potential mechanisms controlling the interactions between these cells were investigated using human alveolar macrophages (AM) and MDCK or A549 epithelial cells. Five percent human serum enhanced the adhesion of AM to MDCK cells by approximately 6-fold and to A549 cells by approximately 1.7-fold. This enhancement was reduced by heating the serum for 30 min at 55 degrees C. Treating normal human serum with methylamine to inactivate C3, substituting C3-deficient serum, or pretreating serum-exposed MDCK cells with anti-C3 F(ab')2 all significantly diminished the adhesion of AM, suggesting that complement is involved. With the use of flow cytometry to examine complement receptors on AM, both CD11b/CD18 and CD11c/CD18 were detected but CR1 was not evident. Preincubating AM with a monoclonal antibody to CD18 reduced the adhesion of AM to MDCK cells by 40% while a significant reduction could not be demonstrated after preincubation with antibodies to either CD11b or CD11c. These data suggest that in the presence of serum C3bi is deposited on the surface of MDCK cells and that AM may attach to these cells, at least in part, through interactions between C3bi and one or more receptors in the CD11/CD18 family, which are present on AM.