Effect of Tamm-Horsfall urinary glycoprotein on phagocytosis and killing of type I-fimbriated Escherichia coli.
Human polymorphonuclear leukocytes (PMN) ingest type I (mannose sensitive) fimbriated Escherichia coli even in the absence of antibody, complement, or other serum opsonins. Our studies suggest that the Tamm-Horsfall urinary glycoprotein (THP) interferes with serum-independent ingestion. Electron micrographs showed that dissolved THP adhered to type I fimbriae and formed a pseudocapsule around bacteria bearing type I fimbriae. Phase-variant bacteria grown on blood agar neither expressed fimbriae nor bound THP. Affinity column chromatography demonstrated mannose-sensitive binding between purified type I fimbriae and purified THP. The ability of human PMN to bind and ingest type I-fimbriated E. coli was diminished if the bacteria had been coated by exposure to THP at physiologic concentrations. At 1 h, PMN were associated with an average of 2.62 uncoated bacteria, but with only 0.18 coated bacteria (P less than 0.001). alpha-Methyl mannoside blocked the observed effect of THP on binding and phagocytosis in a dose-dependent fashion: increased mannoside led to increased blocking. PMN preincubated with THP were able to bind and phagocytose normally. There did not appear to be any significant clumping of bacteria in suspension to account for these effects. Bactericidal assays with leukocytes in suspension demonstrated protection of THP-coated bacteria. At 1 h, PMN killed 42% of noncoated E. coli (a decrease of 0.24 log), but the number of THP-coated bacteria increased by 75% (an increase of 0.24 log). These observations may partially explain the virulence of E. coli in the bladder and kidney, where serum activity is low and THP is abundant.
Kuriyama
S M
SM
Silverblatt
F J
FJ
D000268:Adhesiveness; D002478:Cells, Cultured; D004926:Escherichia coli / Q000276:immunology*; D010861:Fimbriae, Bacterial; D006801:Humans; D008362:Mannosides / Q000494:pharmacology; D008766:Methylmannosides; D009088:Mucoproteins / Q000302:isolation & purification / Q000502:physiology*; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis; D011485:Protein Binding; D058949:Uromodulin
D008362:Mannosides; D008766:Methylmannosides; D009088:Mucoproteins; C548612:UMOD protein, human; D058949:Uromodulin; C008466:methylmannoside