Transient neutropenia increases macrophage accumulation and cell proliferation but does not improve repair following intratendinous rupture of Achilles tendon.

Abstract

Neutrophils are the first leukocytes to invade tendons after an acute injury. They could modulate both the inflammatory response and early repair processes through the release of reactive species, cytokines, growth factors, and proteinases. However, the exact role of these cells in damaged tendons remains unclear. We investigated their role by inducing a transient neutropenia in C57BL/6 male mice using an anti-Ly6C/Ly6G antibody. Placebo mice received only serum. The right Achilles tendon was sectioned and sutured using the 8-strand technique, which allowed immediate weight bearing. A significant increase in macrophage accumulation and cell proliferation was observed in tendons from neutropenic animals compared to the placebo group at days 3 and/or 7 postinjury. However, there was a reduction in cell proliferation in a group of mice depleted in macrophages, indicating that macrophages play a role in cell replication in injured tendons. Lastly, the tendons of neutropenic and placebo mice had similar collagen content and mechanical properties at days 7, 14, and/or 28 postinjury. Our findings demonstrate that neutropenia modulates macrophage accumulation and cell proliferation, but overall, a reduction in neutrophil number has no significant effect on tendon repair.