ICAM-1 mediates surface contact between neutrophils and keratocytes following corneal epithelial abrasion in the mouse

Abstract

Corneal epithelial abrasion elicits an inflammatory response involving neutrophil (PMN) recruitment from the limbal vessels into the corneal stroma. These migrating PMNs make surface contact with collagen and stromal keratocytes. Using mice deficient in PMN integrin CD18, we previously showed that PMN contact with stromal keratocytes is CD18-dependent, while contact with collagen is CD18-independent. In the present study, we wished to extend these observations and determine if ICAM-1, a known ligand for CD18, mediates PMN contact with keratocytes during corneal wound healing. Uninjured and injured right corneas from C57Bl/6 wild type (WT) mice and ICAM-1 −/− mice were processed for transmission electron microscopy and imaged for morphometric analysis. PMN migration, stromal thickness, and ICAM-1 staining were evaluated using light microscopy. Twelve hours after epithelial abrasion, PMN surface contact with paralimbal keratocytes in ICAM-1 −/− corneas was reduced to ~50% of that observed in WT corneas; PMN surface contact with collagen was not affected. Stromal thickness (edema), keratocyte network surface area and keratocyte shape were similar in ICAM-1 −/− and WT corneas. WT keratocyte ICAM-1 expression was detected at baseline and ICAM-1 staining intensity increased following injury. Since ICAM-1 is readily detected on mouse keratocytes and PMN-keratocyte surface contact in ICAM-1 −/− mice is markedly reduced, the data suggest PMN adhesive interactions with keratocyte stromal networks is in part regulated by keratocyte ICAM-1 expression.

Topical Neutralization of Interleukin-17 during Experimental Pseudomonas aeruginosa Corneal Infection Promotes Bacterial Clearance and Reduces Pathology

“…After scratch injury alone (without infection), neutrophils recruited from the limbal vessels into the corneal stroma make ICAM-1-mediated surface contact with stromal keratinocytes, and ICAM-1 KO mice demonstrate decreased stromal infiltration (12). In P. aeruginosa keratitis after scratch injury, Hazlett and coworkers reported that ICAM-1-deficient mice had less-severe corneal opacities (as we observed) but similar neutrophil numbers and inflammatory cell infiltration on histopathology (17), which is different from our findings.…”

Targeting Imbalance between IL-1β and IL-1 Receptor Antagonist Ameliorates Delayed Epithelium Wound Healing in Diabetic Mouse Corneas

“…Neutrophils 31 and NK cells 32 have been shown to play a role in corneal epithelium-wound healing, stromal remolding, and nerve regeneration. We next investigated whether their infiltrations were altered in DM healing corneas and the effects of IL-1Ra herein.…”

“…54 Neutrophils have been shown to act as an early response immune cells that play a key role in the healing of an epithelium-debridement wound. 31 A large number of NK cells infiltrate into the cornea and participate in the modulation of Figure 9 Schematic diagram deciphering the role of balanced IL-1beIL-1 receptor antagonist (IL-1Ra) signaling in mediating epithelial wound healing and its defects in the diabetic corneas. A: In the normal corneas, epithelium injury causes the release of alarmins (eg, high mobility group box 1 protein), which activates Toll-like receptors (TLRs), resulting in the initial induction of IL-1b and the secreted form of IL-1Ra (sIL-1Ra).…”

γδ T cells regulate the expression of cytokines but not the manifestation of fungal keratitis

“…In the Aspergillus fumigates infected lung, CXCR2 recruits neutrophils to the infection site (Bonnett et al, 2006). In the cornea, ICAM-1, MIP-2 and other cytokines have a role in attracting neutrophils to the inflammatory site (Gagen et al, 2010;Zaidi et al, 2012;Tripathi et al, 2013). However, the regulator of neutrophil infiltration in FK is unknown.…”