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C. Kao, T.–I. Chikama, C.–Y. Liu, S.A. K. Harvey, M.L. Funderburgh, J.L. Funderburgh, W.W. Kao; Lumican Serves as a Substratum for PMN Formation and Migration during Myelopoiesis and Corneal Wound Healing . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2130.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Lumican null mice suffered delayed healing of corneal epithelium debridement. Our present studies further investigate the role of lumican on inflammatory response during corneal wound healing and formation of PMN (polymorphonuclear neutrophils) during myelopoiesis. Methods: Inflammatory responses of corneal epithelium debridement (2 mm in diameter) were compared in 2 months–old knock out mice lacking lumican (Lum–/–), keratocan (Kera–/–), and Kera–Lum/Lum–/– bitransgenic mice. Wild type (Lum+/+) mice were used as control. A two chamber assay using fMLP as a chemotactant was used to elucidate the role of lumican on the cell migration of PMN from Lum+/+ and Lum–/– mice. Microarray analysis (Affymetrix GeneChip) was performed to compare the mRNA profiles of PMN isolated from Lum+/+ and Lum–/– mice. Results: The epithelium debridement of Lum–/– mice healed (in 48 h) slower than the wild type mice (in 24 h). Histological examination revealed that in wild type and Kera–/– mice, inflammatory cells appeared in stroma at the leading edge of the migrating epithelium at 12 hours after wounding and the number of PMN reached a peak in 24 hours. The PMN invasion was significantly retarded in the injured corneas of Lum–/– mice in comparison to wild type mice. Whereas in compound Kera–Lum/Lum–/– transgenic mice, infiltration of inflammatory cells was delayed and could be found at the central denuded cornea in 24 h at a time lumican was detected by immunohistochemistry. Chemotactic analysis with fMLP indicated that lumican coated surface facilitated the migration of both Lum+/+ and Lum–/– PMN, but the latter showed impaired response to the chemotactant. Microarray analysis revealed the down regulation of Gpr33, a receptor of formyl peptides.Conclusions:Our results suggest that lumican modulates inflammatory response by serving as a substratum for PMN migration and a regulatory factor for the formation of PMN during myelopoiesis.
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