title: New insights into the possible role of bacteriophages in host defense and disease.
abstract: BACKGROUND: While the ability of bacteriophages to kill bacteria is well known and has been used in some centers to combat antibiotics - resistant infections, our knowledge about phage interactions with mammalian cells is very limited and phages have been believed to have no intrinsic tropism for those cells. PRESENTATION OF THE HYPOTHESIS: At least some phages (e.g., T4 coliphage) express Lys-Arg-Gly (KGD) sequence which binds beta3 integrins (primarily alphaIIbbeta3). Therefore, phages could bind beta3+ cells (platelets, monocytes, some lymphocytes and some neoplastic cells) and downregulate activities of those cells by inhibiting integrin functions. TESTING THE HYPOTHESIS: Binding of KGD+ phages to beta3 integrin+ cells may be detected using standard techniques involving phage - mediated bacterial lysis and plaque formation. Furthermore, the binding may be visualized by electron microscopy and fluorescence using labelled phages. Binding specificity can be confirmed with the aid of specific blocking peptides and monoclonal antibodies. In vivo effects of phage - cell interactions may be assessed by examining the possible biological effects of beta3 blockade (e.g., anti-metastatic activity). IMPLICATION OF THE HYPOTHESIS: If, indeed, phages can modify functions of beta3+ cells (platelets, monocytes, lymphocytes, cancer cells) they could be important biological response modifiers regulating migration and activities of those cells. Such novel understanding of their role could open novel perspectives in their potential use in treatment of cardiovascular and autoimmune disease, graft rejection and cancer.
authors.affiliation: L,Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland. agorski@ikp.pl
authors.forename: Andrzej
authors.initials: A
authors.lastname: Gorski
authors.forename: Krystyna
authors.initials: K
authors.lastname: Dabrowska
authors.forename: Kinga
authors.initials: K
authors.lastname: Switala-Jeleń
authors.forename: Maria
authors.initials: M
authors.lastname: Nowaczyk
authors.forename: Beata
authors.initials: B
authors.lastname: Weber-Dabrowska
authors.forename: Janusz
authors.initials: J
authors.lastname: Boratynski
authors.forename: Joanna
authors.initials: J
authors.lastname: Wietrzyk
authors.forename: Adam
authors.initials: A
authors.lastname: Opolski