Scientists present new data on how bacterial molecules interact with blood cells. The findings can help better understand what happens when bacteria are in the blood vessels. It has importance for the treatment of sepsis and inflammation.
Despite our current knowledge of biochemistry and molecular biology of the human body, there are still processes that are poorly understood and may have medical importance. For example, haemostasis — which aims to keep the blood within a damaged blood vessel — is associated with certain blood cells called platelets. Such cells may interact with bacteria which cause dangerous inflammation. In plain words, there is a connection between inflammation and blood clotting, but the exact molecular mechanisms remain insufficiently investigated. A group of scientists including Sechenov University members decided to fill this gap and published their recent study in Scientific Reports.
The researchers turned their attention to bacterial lipopolysaccharides — large molecules consisting of a lipid and a carbohydrate, that are found in the outer membrane of gram-negative bacteria. Lipopolysaccharides — strong mediators of bacterial sepsis — are recognised by the toll-like receptor 4 (TLR4) which is expressed on the surface of granulocytes, monocytes, dendric cells, and platelets — anucleate blood cells responsible for haemostasis.
For the purposes of this study, the medics collected blood from healthy volunteers, 23 males and 17 females, aged 18–35. Most experiments involved the samples of polymorphonuclear leukocytes prepared from the whole blood. The samples were tested by flow cytometry for in vitro interaction with lipopolysaccharides and platelet aggregation. Thrombus growth assays and immunoblotting were employed as well.
The authors found that lipopolysaccharides induced polymorphonuclear leukocyte activation by CD11b. It means that, indeed, there was an interaction between these molecules and the cells. In another set of experiments, lipopolysaccharides increased phosphorylation of IKκB in polymorphonuclear leukocytes, as well as the number of their aggregates with platelets in washed cell suspensions. On the other hand, lipopolysaccharides did not considerably affect thrombus growth or platelet aggregation.
The authors note that the effects require further investigation, mainly because the lipopolysaccharide-mediated weak inhibition of platelet activation, observed in the experiments, could occur via a mechanism potentially involving cAMP/cGMP signalling. At the same time, the platelets could potentially respond to low doses of ADP. The researchers hope to find the answers in their future works.
This study was conducted by the Department of Normal Physiology, Sechenov University, together with the Centre of Theoretical Problems of Physico-Chemical Pharmacology (Moscow), Rogachev National Medical Research Centre of Paediatric Haematology, Oncology and Immunology (Moscow), the Institute of Biochemical Physics (Moscow), the Department of Physics at the Lomonosov Moscow State University (Moscow), and Sechenov Institute of Evolutionary Physiology and Biochemistry (St Petersburg).