Adherence of Pseudomonas aeruginosa to cells of the respiratory tract of patients with cystic fibrosis (CF) appears to be a necessary precondition for colonization and infection. To date no effective anti-adhesive strategy has been devised for preventing P. aeruginosa infection in these vulnerable hosts. The purpose of these studies was to evaluate the potential for preventing adhesion of P. aeruginosa to epithelial cells with dextran. Dextran (3,000-70,000 MW) inhibited adhesion of P. aeruginosa to buccal and A549 pulmonary epithelial cells; the 3,000 MW compound, at 10 mM was most inhibitory. Adhesion was inhibited optimally at pH 7.4 and was independent of charge; dextran and dextran sulfate were equally inhibitory. Dextran was most inhibitory if added to the epithelial cells before the P. aeruginosa; adhesion was reversed only minimally by adding dextran after the bacteria were bound. The inhibitory effect appeared to be nonspecific because other neutral polysaccharides (glycogen and mannan) were also inhibitory, dextran blocked attachment of other respiratory tract pathogens (Staphylococcus aureus, Group A streptococcus, and Haemophilus influenzae), and because dextran did not bind specifically to bacteria or to epithelial cells. Dextran is an inexpensive and nontoxic agent and may be useful in patients with CF to prevent colonization and infection with P. aeruginosa.

Glucose has previously been shown to increase the in vitro phagocytosis of unopsonized Pseudomonas aeruginosa by freshly explanted murine peritoneal macrophages (PM) and cultivated alveolar macrophages (AM). This study examined the effect of glucose on the same phagocytosis process in human AM in order to determine whether this phenomenon is conserved among species. Freshly explanted human AM phagocytosed unopsonized P. aeruginosa at a low level (2 bacteria/macrophage/30 min), whereas mouse AM ingested a negligible number of P. aeruginosa (0.01 bacterium/macrophage/30 min). Glucose had no effect on this or other phagocytic processes in freshly explanted mouse or human AM. However, following in vitro cultivation for 72 h, human AM phagocytosed three to four times more unopsonized P. aeruginosa than did freshly explanted cells, but only in the presence of glucose. This glucose-inducible phagocytic response had also been observed in cultivated murine AM. Although similar increases were also detected for the phagocytosis of latex particles and complement-coated sheep erythrocytes by cultivated human AM, these processes were not glucose dependent. The lack of response to glucose in freshly explanted mouse AM was attributed to insufficient glucose transport; however, freshly explanted human AM exhibited significant facilitative glucose transport activity that was inhibitable by cytochalasin B and phloretin. Taken together, these results suggest that the process of glucose-inducible phagocytosis of unopsonized P. aeruginosa is conserved among macrophages from different species, including humans, and that AM, but not PM, required cultivation for this glucose effect to occur. Glucose transport by AM appears to be necessary but not sufficient for phagocytosis of unopsonized P. aeruginosa.