title: Wound healing characteristics of ICAM-1 null mice devoid of all isoforms of ICAM-1.
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.
authors.affiliation: Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Andre N
authors.initials: AN
authors.lastname: Gay
authors.forename: Oren P
authors.initials: OP
authors.lastname: Mushin
authors.forename: David A
authors.initials: DA
authors.lastname: Lazar
authors.forename: Bindi J
authors.initials: BJ
authors.lastname: Naik-Mathuria
authors.forename: Ling
authors.initials: L
authors.lastname: Yu
authors.forename: Andre
authors.initials: A
authors.lastname: Gobin
authors.forename: C Wayne
authors.initials: CW
authors.lastname: Smith
authors.forename: Oluyinka O
authors.initials: OO
authors.lastname: Olutoye
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D004548:Elasticity; D054459:Elasticity Imaging Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D007536:Isomerism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012867:Skin / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing / Q000502:physiology*
chemical_list: C090509:Icam1 protein, mouse; D018799:Intercellular Adhesion Molecule-1