Platelet and Erythrocyte Extravasation across Inflamed Corneal Venules Depend on CD18, Neutrophils, and Mast Cell Degranulation

Int J Mol Sci. 2021 Jul 8;22(14):7360. doi: 10.3390/ijms22147360.


Platelet extravasation during inflammation is under-appreciated. In wild-type (WT) mice, a central corneal epithelial abrasion initiates neutrophil (PMN) and platelet extravasation from peripheral limbal venules. The same injury in mice expressing low levels of the β2-integrin, CD18 (CD18hypo mice) shows reduced platelet extravasation with PMN extravasation apparently unaffected. To better define the role of CD18 on platelet extravasation, we focused on two relevant cell types expressing CD18: PMNs and mast cells. Following corneal abrasion in WT mice, we observed not only extravasated PMNs and platelets but also extravasated erythrocytes (RBCs). Ultrastructural observations of engorged limbal venules showed platelets and RBCs passing through endothelial pores. In contrast, injured CD18hypo mice showed significantly less venule engorgement and markedly reduced platelet and RBC extravasation; mast cell degranulation was also reduced compared to WT mice. Corneal abrasion in mast cell-deficient (KitW-sh/W-sh) mice showed less venule engorgement, delayed PMN extravasation, reduced platelet and RBC extravasation and delayed wound healing compared to WT mice. Finally, antibody-induced depletion of circulating PMNs prior to corneal abrasion reduced mast cell degranulation, venule engorgement, and extravasation of PMNs, platelets, and RBCs. In summary, in the injured cornea, platelet and RBC extravasation depends on CD18, PMNs, and mast cell degranulation.

Keywords: extravasation; inflammation; platelets.

MeSH terms

  • Animals
  • Blood Platelets / physiology*
  • CD18 Antigens / deficiency
  • CD18 Antigens / physiology*
  • Cell Degranulation*
  • Cell Movement
  • Chemotaxis, Leukocyte
  • Cornea / blood supply*
  • Corneal Injuries / metabolism
  • Corneal Injuries / pathology
  • Epithelium, Corneal / physiology
  • Erythrocytes / physiology*
  • Female
  • Hyperemia / blood
  • Hyperemia / physiopathology*
  • Macrophages / physiology
  • Male
  • Mast Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Microcirculation
  • Microscopy, Electron
  • Models, Animal
  • Neutrophils / physiology*
  • Phagocytosis
  • Regeneration / physiology
  • Transendothelial and Transepithelial Migration / physiology*
  • Vasculitis / blood
  • Vasculitis / immunology*
  • Venules / metabolism*
  • Venules / pathology
  • Wound Healing / physiology


  • CD18 Antigens