Loading...
Pneumolysin induces platelet destruction, not platelet activation, which can be prevented by immunoglobulin preparations in vitro.
Jahn, Kristin Handtke, Stefan Palankar, Raghavendra Weißmüller, Sabrina Nouailles, Geraldine Kohler, Thomas P Wesche, Jan Rohde, Manfred Heinz, Corina Aschenbrenner, Axel F
Jahn, Kristin
Handtke, Stefan
Palankar, Raghavendra
Weißmüller, Sabrina
Nouailles, Geraldine
Kohler, Thomas P
Wesche, Jan
Rohde, Manfred
Heinz, Corina
Aschenbrenner, Axel F
Files
Loading...
Open Access publication
Adobe PDF, 1.71 MB
Other Titles
Abstract
Community-acquired pneumonia by primary or superinfections with Streptococcus pneumoniae can lead to acute respiratory distress requiring mechanical ventilation. The pore-forming toxin pneumolysin alters the alveolar-capillary barrier and causes extravasation of protein-rich fluid into the interstitial pulmonary tissue, which impairs gas exchange. Platelets usually prevent endothelial leakage in inflamed pulmonary tissue by sealing inflammation-induced endothelial gaps. We not only confirm that S pneumoniae induces CD62P expression in platelets, but we also show that, in the presence of pneumolysin, CD62P expression is not associated with platelet activation. Pneumolysin induces pores in the platelet membrane, which allow anti-CD62P antibodies to stain the intracellular CD62P without platelet activation. Pneumolysin treatment also results in calcium efflux, increase in light transmission by platelet lysis (not aggregation), loss of platelet thrombus formation in the flow chamber, and loss of pore-sealing capacity of platelets in the Boyden chamber. Specific anti-pneumolysin monoclonal and polyclonal antibodies inhibit these effects of pneumolysin on platelets as do polyvalent human immunoglobulins. In a post hoc analysis of the prospective randomized phase 2 CIGMA trial, we show that administration of a polyvalent immunoglobulin preparation was associated with a nominally higher platelet count and nominally improved survival in patients with severe S pneumoniae-related community-acquired pneumonia. Although, due to the low number of patients, no definitive conclusion can be made, our findings provide a rationale for investigation of pharmacologic immunoglobulin preparations to target pneumolysin by polyvalent immunoglobulin preparations in severe community-acquired pneumococcal pneumonia, to counteract the risk of these patients becoming ventilation dependent. This trial was registered at www.clinicaltrials.gov as #NCT01420744.
Citation
Blood Adv. 2020 Dec 22;4(24):6315-6326. doi: 10.1182/bloodadvances.2020002372.
Publisher
Journal
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
EISSN
2473-9537
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution 4.0 International