(102) Sex Differences in Platelet-Immune Responses in a Murine Model of Psychological Stress

Introduction/Rationale: Psychological stress is associated with systemic inflammation and platelet activation. Activated platelets serve important immune functions, such as recruiting leukocytes to sites of inflammation, but the responses of platelets and leukocytes to psychological stress are incompletely understood.

Methods: To induce psychological stress, young adult female and male C57BL/6J mice were exposed to restraint and predator scent two hours daily for three consecutive days, and compared to unmanipulated controls (n=10 per group). Effectiveness of the paradigm was confirmed by measuring corticosterone in feces and epinephrine in urine by ELISA at the final stressor. Body weight was compared before and two days after the stress paradigm. Platelet P-selectin and MHC-I expression were measured by flow cytometry two hours after the stress paradigm. Complete blood cell counts and flow cytometric analysis of circulating monocyte CD11b and CCR5 expression were performed two days or one week after the stress paradigm. Statistical analysis was conducted by Mann-Whitney U test with significance set at alpha = 0.05.

Results: Stress increased corticosterone levels and induced weight loss in both male and female mice, but epinephrine was increased in male mice only. Platelet P-selectin and MHC-I expression were increased approximately twofold in stressed males, and accompanied by a threefold decrease in circulating CD11b+ and CCR5+ classical monocytes within two days of the stress paradigm. Female mice did not demonstrate platelet activation, and a decrease in circulating CD11b+ and CCR5+ classical monocytes was not noted until one week after application of stress.

Conclusion: These data demonstrate sex differences in platelet-immune responses to psychological stress. Given that epinephrine potentiates platelet activation, further studies will query if epinephrine-driven platelet activation in male mice contributes to redistribution of activated monocytes out of the blood in the context of psychological stress.