Effect of leukocytes on corneal cellular proliferation and wound healing.

PURPOSE To establish whether fucoidin, by blocking the adhesion of leukocytes on the limbal vascular endothelium, prevents extravasation of the cells from the blood stream into the limbal stroma and the wounded area after corneal injury. Successful leukocyte blocking enabled investigation of the influence of leukocytes on corneal cellular proliferation after corneal wounding. METHODS Thirty-two New Zealand White rabbits were used. Photorefractive keratectomy (PRK) and a standardized alkali corneal wound were used as models in two sets of experiments. In half of the injured rabbits fucoidin was used to prevent leukocytes from leaving the local vessels. The efficiency of the blocking technique was evaluated by counting the number of leukocytes in the limbal and wounded corneal areas. Proliferating cell nuclear antigen (PCNA) was used as a marker for proliferative activity. RESULTS The infiltration of leukocytes into the limbus and the cornea after PRK and alkali injuries can be blocked by fucoidin. The healing rate of corneal epithelium after alkali burn was retarded in the absence of leukocytes. PCNA expression was enhanced in the presence of leukocytes. Fucoidin per se had no influence on corneal cell proliferation and wound healing. CONCLUSIONS Polymorphonuclear leukocytes (PMNs) can be prevented from entering the cornea in vivo by fucoidin after PRK and after alkali burn. The corneal epithelial healing rate is delayed in the absence of PMNs in vivo, and PCNA expression increases in the presence of leukocytes.

[1]  S. Seregard,et al.  Proliferating cell nuclear antigen colocalization with corneal epithelial stem cells and involvement in physiological cell turnover. , 2009, Acta ophthalmologica Scandinavica.

[2]  P. Fagerholm,et al.  Expression of proliferating cell nuclear antigen in corneas kept in long term culture. , 1998, Acta ophthalmologica Scandinavica.

[3]  M. Reim,et al.  The cornea surface and wound healing , 1997, Progress in Retinal and Eye Research.

[4]  B. Imhof,et al.  To stick or not to stick: the new leukocyte homing paradigm. , 1996, Current opinion in cell biology.

[5]  D. Maurice,et al.  Inflammatory cells, refractive regression, and haze after excimer laser PRK. , 1996, Journal of refractive surgery.

[6]  T Seiler,et al.  Excimer laser photorefractive keratectomy. , 1995, Survey of ophthalmology.

[7]  Pablo Engel,et al.  The selecting: vascular adhesion molecules , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  J. May,et al.  Reduction of Burn Injury by Inhibiting CD18‐Mediated Leukocyte Adherence in Rabbits , 1994, Plastic and reconstructive surgery.

[9]  F. Calzetti,et al.  Interleukin 10 (IL-10) upregulates IL-1 receptor antagonist production from lipopolysaccharide-stimulated human polymorphonuclear leukocytes by delaying mRNA degradation , 1994, The Journal of experimental medicine.

[10]  G. Trinchieri,et al.  Cytokine cross‐talk between phagocytic cells and lymphocytes: Relevance for differentiation/activation of phagocytic cells and regulation of adaptive immunity , 1993, Journal of cellular biochemistry.

[11]  W. Kao,et al.  Effects of Polymorphonuclear Neutrophils on Protein Synthesis by Alkali-Injured Rabbit Corneas: A Preliminary Study , 1993, Cornea.

[12]  P. Hedqvist,et al.  Chemoattractant-induced firm adhesion of leukocytes to vascular endothelium in vivo is critically dependent on initial leukocyte rolling. , 1992, Acta physiologica Scandinavica.

[13]  A. Mantovani,et al.  Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products. , 1992, Blood.

[14]  M. Patarroyo Leukocyte adhesion in host defense and tissue injury. , 1991, Clinical immunology and immunopathology.

[15]  Timothy A. Springer,et al.  Adhesion receptors of the immune system , 1990, Nature.

[16]  L. Osborn,et al.  Leukocyte adhesion to endothelium in inflammation , 1990, Cell.

[17]  E. P. Kay,et al.  Corneal Endothelium Modulation Factor Released by Polymorphonuclear Leukocytes , 1990, Investigative ophthalmology & visual science.

[18]  M J Banda,et al.  Wound macrophages express TGF-alpha and other growth factors in vivo: analysis by mRNA phenotyping. , 1988, Science.

[19]  R. Bravo,et al.  Cyclin/PCNA is the auxiliary protein of DNA polymerase-δ , 1987, Nature.

[20]  P. Morméde,et al.  Immunoreactive fibroblast growth factor in cells of peritoneal exudate suggests its identity with macrophage-derived growth factor. , 1985, Biochemical and biophysical research communications.

[21]  C. Paterson,et al.  Sodium citrate reduces the incidence of corneal ulcerations and perforations in extreme alkali-burned eyes--acetylcysteine and ascorbate have no favorable effect. , 1981, Investigative ophthalmology & visual science.

[22]  P. Kulkarni,et al.  The role of arachidonic acid metabolites in the mediation of the polymorphonuclear leukocyte response following corneal injury. , 1980, Investigative ophthalmology & visual science.

[23]  R. Ross,et al.  A macrophage-dependent factor that stimulates the proliferation of fibroblasts in vitro. , 1976, The American journal of pathology.

[24]  R. Ross,et al.  The neutrophilic leukocyte in wound repair a study with antineutrophil serum. , 1972, The Journal of clinical investigation.

[25]  W. Altemeier,et al.  Stimulants of cellular proliferation in wounds. , 1971, Archives of surgery.

[26]  R. Ross THE FIBROBLAST AND WOUND REPAIR , 1968, Biological reviews of the Cambridge Philosophical Society.

[27]  J. Dunphy,et al.  Wound healing. I. Injury and normal repair. , 1958, The New England journal of medicine.

[28]  Dunphy Je,et al.  Wound healing. I. Injury and normal repair. , 1958 .

[29]  Weimar,et al.  POLYMORPHONUCLEAR INVASION OF WOUNDED CORNEAS , 1957, The Journal of experimental medicine.

[30]  A. Carrel GROWTH-PROMOTING FUNCTION OF LEUCOCYTES , 1922, The Journal of experimental medicine.

[31]  M. Wagoner Chemical injuries of the eye: current concepts in pathophysiology and therapy. , 1997, Survey of ophthalmology.

[32]  M. Cassatella The production of cytokines by polymorphonuclear neutrophils. , 1995, Immunology today.

[33]  Z. Zhu [Inflammatory mechanisms in corneal ulceration]. , 1990, [Zhonghua yan ke za zhi] Chinese journal of ophthalmology.