Delayed Wound Healing in the Absence of Intercellular Adhesion Molecule-1 or L-Selectin Expression

Abstract

Inflammatory cells play a crucial role in wound healing, but the role of adhesion molecules including L-selectin and intercellular adhesion molecule-1 (ICAM-1) is not known in this process. We examined skin wound repair of excisional wounds in mice lacking L-selectin, ICAM-1, or both. The loss of ICAM-1 inhibited wound healing, keratinocyte migration from the edges of the wound toward the center, and granulation tissue formation. By contrast, L-selectin deficiency alone did not affect any of these parameters. However, the loss of both L-selectin and ICAM-1 resulted in inhibition of keratinocyte migration and granulation tissue formation beyond those caused by loss of ICAM-1 alone. Treatment of platelet-derived growth factor to the wounds normalized delayed wound healing in ICAM-1(-/-) mice, but not in L-selectin/ICAM-1(-/-) mice. Therefore, although ICAM-1 contributes to wound repair to a greater extent than L-selectin, a role for L-selectin was revealed in the absence of ICAM-1. The impaired wound repair was associated with reduced infiltration of neutrophils and macrophages in ICAM-1(-/-) and L-selectin/ICAM-1(-/-) mice. These results demonstrate a distinct role of ICAM-1 and L-selectin in wound healing and that the delayed wound healing in the absence of these molecules is likely because of decreased leukocyte accumulation into the wound site.

Femur window—a new approach to microcirculation of living bone in situ

“…Measurement of these parameters are not only essential to monitor the absence of local inflammation in bone chamber implants but also necessary to understand the complex interactions of the microenvironment in bone tissue. Several observations confirm that leukocytes play an important role in fracture repair and wound healing and a disturbance of leukocyte homeostasis in tissue leads to impairment of tissue regeneration [5,6,26,41,44]. Here we present for the first time the time-dependent alterations in interactions between leukocytes and endothelium of bone vessels quantitatively, following a surgical procedure to bone.…”

Intercellular Adhesion Molecule-1 and L-Selectin Regulate Bleomycin-Induced Lung Fibrosis

“…This is consistent with the finding that L-selectin and ICAM-1 function cooperatively to mediate optimal leukocyte rolling as well as to recruit leukocytes into inflammatory sites. 10,15,18 More importantly, bleomycin-induced pulmonary fibrosis was nearly eliminated in the absence of both ICAM-1 and L-selectin expression ( Figures 2 and 3). Therefore, the present study reveals a critical and cooperative role of L-selectin and ICAM-1 in the development of bleomycin-induced pulmonary fibrosis.…”

“…12,16 -18 Furthermore, L-selectin and ICAM-1 function synergistically to mediate optimal leukocyte rolling and entry into inflammatory sites, which is essential for the generation of inflammatory responses in vivo. 10,15,18 Despite a critical role of inflammatory cell infiltration in the bleomycin-induced pulmonary fibrosis, studies investigating the contribution of adhesion molecules to this model are limited. Bleomycin-induced pulmonary fibrosis is inhibited in transgenic mice overexpressing soluble E-selectin that inhibits the binding of leukocytes to Eselectin on the endothelium.…”

Differential Roles of Macrophages in Diverse Phases of Skin Repair

“…Furthermore, wounds in the neonatal PU.1 null mouse, which lacks macrophages and neutrophils (but also B cells, mast cells, eosinophils), heal without scar and, surprisingly, with a similar time course as wild-type siblings (13). However, the need of macrophages for physiological repair in adults is supported in recent wound healing studies in various murine knockout models in which impaired wound healing is associated with an attenuated number of macrophages at the wound site (14)(15)(16)(17)(18). Although all of these studies emphasize that leukocytes significantly affect the quality of the healing response, knowledge of these models is limited, because they either do not target pathways mediated exclusively by macrophages or they address a neonate repair response, which is known to differ from healing in the adult organism (19).…”