Endothelial selectins regulate skin wound healing in cooperation with L-selectin and ICAM-1

Area of Science:

• Immunology
• Dermatology
• Cell Biology

Background:

• Skin wound healing is a complex process involving inflammatory cell infiltration, crucial for repair.
• Adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and selectins (L-, E-, P-selectin), play a regulatory role in this infiltration.
• The specific contributions and interactions of these adhesion molecules in wound healing are not fully understood.

Purpose of the Study:

• To investigate the cooperative roles and relative importance of selectins and ICAM-1 in skin wound healing.
• To determine the impact of combined deficiencies or blockades of these adhesion molecules on the healing process.
• To explore potential therapeutic interventions, such as growth factor application, for impaired wound healing.

Main Methods:

• Excisional wound repair was examined in genetically modified mice lacking L-selectin and ICAM-1 (L-selectin/ICAM-1(-/-)).
• Wild-type mice were treated with blockade antibodies against E- and P-selectins.
• Combined genetic deficiency and blockade strategies were employed, alongside growth factor treatments (bFGF, PDGF).

Main Results:

• Mice lacking L-selectin/ICAM-1 or wild-type mice with E-/P-selectin blockade showed delayed wound healing.
• Combined blockade of E- and P-selectins in L-selectin/ICAM-1(-/-) mice led to a more pronounced delay in healing.
• Deficiencies in adhesion molecules suppressed keratinocyte migration, angiogenesis, granulation tissue formation, leukocyte infiltration, and cytokine expression (TGF-β, IL-6).
• Basic fibroblast growth factor (bFGF) significantly improved wound healing in severely impaired models by enhancing leukocyte infiltration, cytokine production, keratinocyte migration, angiogenesis, and collagen synthesis.

Conclusions:

• Skin wound healing is cooperatively regulated by L-selectin, E-selectin, P-selectin, and ICAM-1.
• The combined action of these adhesion molecules is critical for efficient wound repair.
• bFGF demonstrates therapeutic potential for treating delayed wound healing by overcoming the limitations imposed by the absence of these adhesion molecules.