In vitro Immunosuppressive and Anti-Phagocytic Properties of the Exopolysaccharide of Mucoid Strains of <i>Pseudomonas aeruginosa</i>

Abstract

The exopolysaccharide (EPS) of Pseudomonas aeruginosa was found to significantly inhibit neu-trophil random movement, chemotaxis and degranulation at concentrations as low as 0.3 μg/ml. Neutrophil adherence, respiratory burst and bactericidal capacity were inhibited by EPS concentrations of ≥ 3 μg/ml. Similarly, mitogen-induced lymphocyte transformation was more sensitive to the inhibitory effects of EPS than natural-killer cell cytotoxicity. These results cannot be explained by simple mechanical blockade, as additions of EPS as late as 48 h after the initiation of lymphocyte cultures still resulted in a significant inhibition of lymphocyte transformation. However, the inhibitory effects of EPS can be reversed by extensive washing of treated lymphocytes. These results suggest that the propensity of mucoid P. aeruginosa to persist in cystic fibrosis may be explained in part by the ability of EPS to interfere with host immunity.

Effect of <i>Pseudomonas aeruginosa</i> on lnterleukin-8 Release from Human Phagocytes

“…Mucoid in contrast to nonmucoid P. aeruginosa strains failed to induce the chemotactically active LTB4 [20,25]. Thus, we compared the capacity of CF3 and CF3M strains to induce IL-8 from PMN and PBMC.…”

“…IL-8 triggers the following main responses in neutrophils, its major target cell: shape change and transendothelial migration, degranulation, and a respiratory burst [4,5], P. aeruginosa is an opportunistic pathogen which causes either localized infections such as pneumonia in patients with CF or generalized septicemia in immunocompromised hosts suffering from severe burns, cancer, or receiving im munosuppressive therapy [11.12]. A predominant feature of P. aeruginosa in CF is the production of alginate, the mu coid exopolysaccharide [3,[13][14][15][16], Alginate mediates an in creased binding of P aeruginosa to epithelial cells, inhibits phagocytosis of mucoid P. aeruginosa bacteria by human granulocytes as well as by human monocytes, the chemotaxis of granulocytes to the inflammatory area, and inhibits opsonization of bacteria [17][18][19][20][21][22]. Previously, we have dem onstrated that P aeruginosa strains from burn patients are potent inducers of LTB4 generation [9], In contrast, the mu coid P. aeruginosa isolates from patients with CF failed to induce LTB4 generation [20], Moreover, mucoid P. aerugi nosa strains from CF patients unlike their nonmucoid revertants led to a reduced LTB., formation on subsequent stimulation [10].…”

“…A predominant feature of P. aeruginosa in CF is the production of alginate, the mu coid exopolysaccharide [3,[13][14][15][16], Alginate mediates an in creased binding of P aeruginosa to epithelial cells, inhibits phagocytosis of mucoid P. aeruginosa bacteria by human granulocytes as well as by human monocytes, the chemotaxis of granulocytes to the inflammatory area, and inhibits opsonization of bacteria [17][18][19][20][21][22]. Previously, we have dem onstrated that P aeruginosa strains from burn patients are potent inducers of LTB4 generation [9], In contrast, the mu coid P. aeruginosa isolates from patients with CF failed to induce LTB4 generation [20], Moreover, mucoid P. aerugi nosa strains from CF patients unlike their nonmucoid revertants led to a reduced LTB., formation on subsequent stimulation [10]. In this regard, alginate, the mucoid exopolysaccharidc, has been described as the component respon sible for the reduced LTB4 generation.…”

Effect of <i>Pseudomonas aeruginosa</i> Alginate on <i>Escherichia col</i><i>i</i>- and <i>Staphylococcus aureu</i><i>s</i>-lnduced Inflammatory Mediator Release from Human Cells

“…12]. Alginate exhibits several fea tures such as an increased binding of P aeruginosa to epi-thelial cells, it inhibits phagocytosis of mucoid P aerugi nosa bacteria by human granulocytes, the chcmotaxis of granulocytes to the inflammatory area, as well as the opso nization of bacteria [13][14][15][16], Another puzzling factor is that the serious lung disease in CF usually can be linked to the presence of a restricted number of pathogens, e.g. P. aeru ginosa.…”

“…In contrast, mucoid P. aeruginosa isolates from CF patients inhibited nonspecific defense mechanisms such as chemotaxis, phagocytosis, opsonization, release of reactive oxygen me tabolites, and leukotriene generation [4,5,[13][14][15][16]. Quite recently, we presented evidence that indeed alginate in duced, via components of the signal transduction pathway, the suppressive effects on neutrophils [6].…”