INHIBITION OF MACROPHAGE PHAGOCYTOSIS BY PSEUDOMONAS-AERUGINOSA RHAMNOLIPIDS IN-VITRO AND IN-VIVO

Patients with cystic fibrosis often have chronic and ultimately lethal pulmonary infections with Pseudomonas aeruginosa. In order to underst and why these bacteria resist pulmonary clearance, we have investigate d the interaction of P. aeruginosa and phagocytic cells. In an earlier study we reported that sub-lytic concentrations of two glycolipids pr oduced by P. aeruginosa (the mono- and dirhamnolipids) caused structur al changes in human monocyte-derived macrophages, and at lower concent rations inhibited the phagocytosis of Staphylococcus epidermidis by th ese cells. In the present study we demonstrate that rhamnolipids also inhibit the in vitro phagocytosis of both P. aeruginosa and Saccharomy ces cerevisiae by thioglycollate-elicited mouse peritoneal macrophages . Using lucifer yellow to label the lysosomal compartments of macropha ges, we determined that rhamnolipids interfere with the internalizatio n of attached particles and reduce the level of phagosome-lysosome fus ion of internalized targets within macrophages. We also demonstrate th at physiologically relevant concentrations of rhamnolipids injected in tratracheally into rat lungs inhibited the response of alveolar macrop hages to a challenge of zymosan particles in vivo. These studies furth er demonstrate the profound inhibitory effects of P. aeruginosa rhamno lipids on macrophage function and are consistent with our hypothesis t hat the in situ production of these rhamnolipids directly contributes to the persistence of this pathogen in cystic fibrosis patient lungs.