TY - JOUR
T1 - Effect of leukopenia induced by cyclophosphamide on the initial stage of arterial thrombosis in mice
AU - Lee, Kee Ook
AU - Kwon, Il
AU - Nam, Hyo Suk
AU - Park, Youngseon
AU - Kim, Jayoung
AU - Shim, Yeseul
AU - Erdenebileg, Zolzaya
AU - Cha, Myoung Jin
AU - Choi, Hyun Jung
AU - Choi, Hye Yeon
AU - Song, Jae Woo
AU - Heo, Ji Hoe
N1 - Funding Information:
This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education ( NRF-2018R1A2A3074996 ).
Publisher Copyright:
© 2021
PY - 2021/10
Y1 - 2021/10
N2 - Introduction: Leukocytes are found in organizing thrombi and are associated with thrombus growth. However, their role in the initial stage of thrombus formation is not well known. We investigated the role of leukocytes in the early stage of arterial thrombosis by inducing leukopenia. Methods: In this double-blind, randomized, placebo-controlled study, 72 Institute of Cancer Research mice were randomly treated with intraperitoneal 100 mg/kg cyclophosphamide or normal saline. The primary outcome was time to occlusion after FeCl3 treatment. We also compared thrombus size, histological composition, and association with peripheral blood cell counts between cyclophosphamide and control groups. Results: Cyclophosphamide treatment significantly decreased leukocyte counts by 82.8% compared to placebo (P < 0.001). The time to occlusion was significantly longer in the cyclophosphamide group (3.31 ± 1.59 min) than in the control group (2.30 ± 1.14 min; P = 0.003). The immunoreactivity for Ly6G-positive cells, intracellular histone H3, and released histone H3 in thrombi was significantly reduced in the cyclophosphamide group by 92.8%, 50.2%, and 34.3%, respectively. Time to occlusion had a moderate negative correlation with leukocyte count in peripheral blood (r = −0.326, P = 0.022) in the entire group. Conclusions: Cyclophosphamide-induced leukopenia attenuated thrombus formation during the early stage of arterial thrombosis. Our findings suggest the potential role of leukocytes in the initial stage of arterial thrombosis.
AB - Introduction: Leukocytes are found in organizing thrombi and are associated with thrombus growth. However, their role in the initial stage of thrombus formation is not well known. We investigated the role of leukocytes in the early stage of arterial thrombosis by inducing leukopenia. Methods: In this double-blind, randomized, placebo-controlled study, 72 Institute of Cancer Research mice were randomly treated with intraperitoneal 100 mg/kg cyclophosphamide or normal saline. The primary outcome was time to occlusion after FeCl3 treatment. We also compared thrombus size, histological composition, and association with peripheral blood cell counts between cyclophosphamide and control groups. Results: Cyclophosphamide treatment significantly decreased leukocyte counts by 82.8% compared to placebo (P < 0.001). The time to occlusion was significantly longer in the cyclophosphamide group (3.31 ± 1.59 min) than in the control group (2.30 ± 1.14 min; P = 0.003). The immunoreactivity for Ly6G-positive cells, intracellular histone H3, and released histone H3 in thrombi was significantly reduced in the cyclophosphamide group by 92.8%, 50.2%, and 34.3%, respectively. Time to occlusion had a moderate negative correlation with leukocyte count in peripheral blood (r = −0.326, P = 0.022) in the entire group. Conclusions: Cyclophosphamide-induced leukopenia attenuated thrombus formation during the early stage of arterial thrombosis. Our findings suggest the potential role of leukocytes in the initial stage of arterial thrombosis.
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U2 - 10.1016/j.thromres.2021.08.017
DO - 10.1016/j.thromres.2021.08.017
M3 - Article
C2 - 34455128
AN - SCOPUS:85113631360
SN - 0049-3848
VL - 206
SP - 111
EP - 119
JO - Thrombosis Research
JF - Thrombosis Research
ER -
