Abstract
BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) permits leukocyte-endothelial adhesion and transmigration during inflammation. Membrane-bound ICAM-1 knockout mice have been used to understand this molecule's role in wound-healing, but expressed spliced isoforms of ICAM-1 that may have impacted results. We aimed to characterize wound-healing in an ICAM-1 null model devoid of all ICAM-1 isoforms. METHODS: Full-thickness 8-mm wounds were created on C57/BL6 wild-type (n = 24) and ICAM-1 null (n = 24) mice. Wound area was calculated using daily photographs. Histologic samples were harvested on postoperative Days 1, 3, 7, and 14. Wound margins were evaluated for mRNA expression of 13 inflammatory cytokines. A separate group of wild-type and ICAM-1 null mice (n = 24) received full-thickness incisions with tensiometry measured at Day 14. Separately, complete blood counts were measured in unwounded wild-type (n = 4) and ICAM-1 null mice (n = 4). RESULTS: Wound-closure was significantly delayed in ICAM-1 null mice through Day 7 by gross and histologic measurement. mRNA expression of VEGF-A was increased in ICAM-1 null mice on Day 3, although no increase in VEGF-A was observed in the wound bed by immunohistochemistry. ICAM-1 null wounds demonstrated higher stiffness by tensiometry on Day 14 compared to the wild-type (1880 ± 926 kPa versus 478 ± 117 kPa; P < 0.01), and had higher counts of white blood cells (10,009 versus 5720 cells/μL, P < 0.05), neutrophils (2130 versus 630 cells/μL, P < 0.01), and lymphocytes (7130 versus 4,740 cells/μL, P < 0.05). CONCLUSIONS: ICAM-1 null mice demonstrate delayed wound-healing and decreased wound elasticity compared to wild-type controls. This lag, however, was less than observed in earlier membrane-bound ICAM-1 knockouts, suggesting that other ICAM-1 isoforms may promote delayed wound-healing.