Related Experiment Videos
Modulation of leukotriene generation by invasive bacteria
1Lehrstuhl für Medizinische Mikrobiologie und Immunologie, Ruhr-Universität Bochum, Germany.
Abstract:
The effect of invasive bacteria on the release of proinflammatory mediators (oxygen radicals, leukotriene release) from human polymorphonuclear neutrophils was studied. Bacterial stimuli were used including genetically cloned invasive Yersinia enterocolitica strains 108-P (bearing the phagocytosis-resistance plasmid) and 108-C (plasmidless variant), Listeria monocytogenes [SLCC 5779 (inv-) and NCTC 7973 (inv+)] as well as an Escherichia coli K 12 strain (pRI 203) in which the inv gene of Y. pseudotuberculosis was cloned. When human polymorphonuclear granulocytes were studied as target cells the inv+ as well as the inv- strains were phagocytosed to a comparable amount with the exception of the L. monocytogenes strain (inv+). Among the invasive strains E. coli HB 101 (pRI 203) was the most active to trigger polymorphonuclear leucocytes (PMN) for oxygen radical production. Preincubation of the cells with bacteria and subsequent stimulation with the Ca ionophore A23187 or opsonized zymosan suppressed the chemiluminescence response to a different degree. The various bacterial strains did not induce leukotriene release from endogenous arachidonic acid. Subsequent stimulation of the infected cells with Ca ionophore or opsonized zymosan led to an altered pattern of the combined amounts of leukotriene B4 (LTB4), 20-OH- and 20-COOH-LTB4 as well as the ratio of LTB4 versus 20-OH and 20-COOH-LTB4. Infection of the cells also reduced strain dependently the number of LTB4-receptor sites. Our data suggest that bacterial uptake modulates the inflammatory response of granulocytes (e.g. chemiluminescence response, leukotriene generation).
Insights
Invasive bacteria alter human immune cell responses, affecting oxygen radical and leukotriene release. Bacterial uptake modulates granulocyte inflammatory functions, impacting key mediators of inflammation.
Area of Science:
- Immunology
- Microbiology
Background:
- Human polymorphonuclear neutrophils (PMNs) are crucial in innate immunity, responding to bacterial invasion by releasing proinflammatory mediators.
- Understanding how invasive bacteria modulate PMN functions is vital for comprehending host-pathogen interactions and inflammatory processes.
Purpose of the Study:
- To investigate the impact of various invasive bacterial strains on the release of proinflammatory mediators, specifically oxygen radicals and leukotrienes, from human PMNs.
- To determine how bacterial uptake influences PMN activation, mediator production, and receptor expression.
Main Methods:
- Human PMNs were exposed to genetically cloned invasive strains of Yersinia enterocolitica, Listeria monocytogenes, and Escherichia coli.
- Oxygen radical production was assessed via chemiluminescence.
- Leukotriene release and receptor site numbers were quantified following bacterial exposure and subsequent stimulation with Ca ionophore or opsonized zymosan.
Main Results:
- While most bacterial strains were phagocytosed similarly, E. coli HB 101 (pRI 203) most potently triggered oxygen radical production.
- Bacterial preincubation suppressed chemiluminescence responses to secondary stimuli.
- No direct leukotriene release was observed, but subsequent stimulation revealed altered leukotriene profiles and reduced LTB4 receptor sites, dependent on bacterial strain.
Conclusions:
- Bacterial uptake significantly modulates the inflammatory response of human granulocytes.
- This modulation affects key functions including chemiluminescence and leukotriene generation, highlighting a complex interplay between bacteria and host immune cells.