Background
Bone marrow (BM)-derived polymorphonuclear leukocytes (PMNs) and monocytes (MO) induced
by cardiopulmonary bypass (CPB) are highly proteolytic and cause postoperative lung
injury. Although CCL23/Myeloid progenitor inhibitory factor-1 is a human CC chemokine
with potent suppressor effects on myeloid progenitor cells, in vivo inhibitory effects on BM-derived leukocyte kinetics associated with CPB are unknown.
Methods
Two-hour CPB was surgically performed in cynomolgus monkeys and BM-derived leukocytes
kinetics were monitored postoperatively by flow cytometry with 5’-bromo-2’-deoxyuridine
(BrdU) and cytokine ELISA. Monkeys were given CCL23 (n=5) or saline (control, n=5)
intravenously daily for 3 days before BrdU labelling and peripheral blood/bronchoalveolar
lavage fluid (BALF) timepoint sampling to reveal BrdU-labelled cells. Levels of cytokines,
CD11b, and L-selectin were considered leukocytic activation markers.
Results
The CCL23 treatment significantly prolonged BM transit of leukocytes (PMNs, 118.4±11.7–95.5±4.1
hours [control]; MO, 91.6±5.0–62.0±3.0 hours [control]) and reduced their alveolar
appearance. The BM pool size of MO was decreased by CCL23 but PMNs were unaffected.
CD11b, L-selectin expression of PMNs and MO during CPB, and post-surgical increases
of interleukin (IL)-6, IL-8, TNF-α, MCP-1, and PMN elastase in the BALF were not suppressed.
Conclusions
CCL23 treatment slows turnover of PMN and MO progenitors in BM and suppresses their
circulatory release and lung recruitment. CCL23 has inhibitory effects specifically
on the CPB-induced BM response and could hold value for preventing CPB-induced lung
injury.
Keywords
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Article info
Publication history
Published online: January 09, 2023
Accepted:
November 30,
2022
Received in revised form:
November 9,
2022
Received:
June 15,
2022
Identification
Copyright
© 2022 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.
