PD Dr. David Alexander Christian Messerer (Ulm/ DE), Christiane Leonie Knapp (Ulm/ DE), Paul Müller (Ulm/ DE), Adam Omar Khalaf Mohamed (Ulm/ DE), Alexander Sebastian Koller (Ulm/ DE), Laura Stukan (Ulm/ DE), Prof. Dr. Hubert Schrezenmeier (Ulm/ DE), Prof. Dr. Markus Huber-Lang (Ulm/ DE), Lisa Wohlgemuth (Ulm/ DE)
Background
Platelet-activating factor (PAF) is an inflammatory mediator involved in many pathophysiologies such as sepsis or allergies. PAF has the ability to activate both neutrophils and thrombocytes. In the present work, we first describe the response of neutrophils elicited by PAF, then examine how the PAF-induced neutrophil response is dependent on platelet-neutrophil complex (PNC) formation, and finally evaluate potential strategies to modulate PNC formation.
Methods
Following ethical approval (#459/18) and informed written consent, blood was taken from healthy human volunteers (24±3 years). Whole blood was stimulated with buffer control or PAF (1µM) and pharmacological agents as indicated for 15 min. Neutrophil activity and the formation of PNCs was analyzed by flow cytometry. Data are reported as mean ± SD from at least six independent donors.
Results
PAF induced neutrophil activation as shown by an upregulation of CD10, CD11b, and CD66b expression as well as in a rise in phagocytic activity and production of radical oxygen species. Additionally, PAF significantly increased the appearance of PNCs. Anti-CD62P (p-Selectin), Iloprost (a prostacyclin analogue), and Ketanserin (5-HT2 antagonist) prevented the formation of PNCs. When PNCs and neutrophils without platelet satellitism (NT–) were compared, it became evident that PNCs had significantly higher phagocytotic activity and produced more radical oxygen species in unstimulated blood and after the addition of PAF than NT–. However, there was no discernible difference between PNCs and NT–when comparing the analyzed activation markers.
Conclusion
PAF stimulates neutrophil activity, partially in a platelet-dependent manner. Further studies need to elucidate the discrepancy regarding cellular effector functions and activation markers and confirm the findings with other methods and stimuli. Moreover, pharmacological interventions that limit the formation of PNCs might modify an acute inflammatory response, which may have therapeutic value. Likewise, activated platelets might be a tool to enhance neutrophil activity in neutropenic patients.
Offenlegung Interessenkonflikt:
No conflict of interest.