Abstract Number: PB1847
Meeting: ISTH 2020 Congress
Background: Platelets have been shown to play a critical role in host survival after Coxsackievirus B3 (CVB3) infection. Recently, we showed that protease-activated receptor 4 (PAR4), the major thrombin receptor on mouse platelets, contributes to anti-viral responses in mice infected with CVB3 or influenza A virus (IAV). Thrombin stimulation of platelets leads to P-selectin exposure and platelet-leukocyte interaction that participates in innate immune responses.
Aims: To investigate the effect of P-selectin (CD62P) deficiency on CVB3 myocarditis and IAV infection in mice.
Methods: CD62P-/- and wild-type (WT) mice (6-8 weeks old) were infected with 105 pfu of CVB3 (Nancy strain). In addition, mice (8-12 weeks old) were infected with 0.02 HAU influenza A/Puerto Rico/8/1934 (PR/8) virus. Progression of CVB3 myocarditis (day 8) and IAV infection (day 3, 5 and 7) were analyzed.
Results: CD62P deficiency resulted in significant increased CVB3 virus load in hearts of mice at day 8 compared to WT mice. This was associated with increased systemic inflammation measured by elevated white blood cell (WBC) and neutrophil numbers in the blood of CD62P-/- mice 8 days after CVB3 infection compared to WT mice. The more severe myocarditis in CD62P-/- mice resulted in increased mortality compared to WT mice. However, a lack of CD62P did not significantly influence the immune cell numbers (total WBC, neutrophils, lymphocytes, monocytes) in the air space of CD62P-/- mouse lungs 3, 5 or 7 days after IAV infection compared to WT mice. Furthermore, CD62P deficiency had no effect on CXCL1, CXCL2, CCL2 or CCL5 levels in the lung 3, 5 or 7 days compared to WT mice after IAV infection.
Conclusions: CD62P contributes to protection in systemic viral infection, such as CVB3 myocarditis, but is not needed for immune responses in localized IAV infection of the lung.
To cite this abstract in AMA style:Egnatz GJ, Bharathi V, Tatsumi K, Mackman N, Antoniak S. P-selectin (CD62P) Deficiency Is Associated with Increased Coxsackievirus B3 Myocarditis But Not Influenza A Virus Infection in Mice [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/p-selectin-cd62p-deficiency-is-associated-with-increased-coxsackievirus-b3-myocarditis-but-not-influenza-a-virus-infection-in-mice/. Accessed January 26, 2022.
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