title: Protective Role of Surfactant Protein D in Ocular Staphylococcus aureus Infection.
abstract: Staphylococcus aureus is one of the most common pathogens causing keratitis. Surfactant protein D (SP-D) plays a critical role in host defense and innate immunity. In order to investigate the role of SP-D in ocular S. aureus infection, the eyes of wild-type (WT) and SP-D knockout (SP-D KO) C57BL/6 mice were infected with S. aureus (10(7) CFU/eye) in the presence and absence of cysteine protease inhibitor(E64).Bacterial counts in the ocular surface were examined 3, 6, 12, 24 hrs after infection. Bacterial phagocytosis by neutrophils and bacterial invasion in ocular epithelial cells were evaluated quantitatively. S. aureus-induced ocular injury was determined with corneal fluorescein staining. The results demonstrated that SP-D is expressed in ocular surface epithelium and the lacrimal gland; WT mice had increased clearance of S. aureus from the ocular surface (p<0.05) and reduced ocular injury compared with SP-D KO mice. The protective effects of SP-D include increased bacterial phagocytosis by neutrophils (p<0.05) and decreased bacterial invasion into epithelial cells (p<0.05) in WT mice compared to in SP-D KO mice. In the presence of inhibitor (E64), WT mice showed enhanced bacterial clearance (p<0.05) and reduced ocular injury compared to absent E64 while SP-D KO mice did not. Collectively, we concluded that SP-D protects the ocular surface from S. aureus infection but cysteine protease impairs SP-D function in this murine model, and that cysteine protease inhibitor may be a potential therapeutic agent in S. aureus keratitis.
authors.affiliation: Department of Surgery, The State University of New York, Upstate Medical University, Syracuse, New York, United States of America; Departments of Ophthalmology, Zhejiang Medical College Affiliated Zhejiang Hospital, Hangzhou, Zhejiang, P. R. China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Surgery, The State University of New York, Upstate Medical University, Syracuse, New York, United States of America.
authors.forename: Osama
authors.initials: O
authors.lastname: Abdel-Razek
authors.affiliation: Department of Pediatrics and the Cardiovascular Research Institute, University of California, San Francisco, California, United States of America.
authors.forename: Samuel
authors.initials: S
authors.lastname: Hawgood
authors.affiliation: Department of Surgery, The State University of New York, Upstate Medical University, Syracuse, New York, United States of America.
authors.forename: Guirong
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D057056:Cysteine Proteases / Q000378:metabolism; D004847:Epithelial Cells / Q000382:microbiology / Q000473:pathology; D005123:Eye / Q000378:metabolism* / Q000382:microbiology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism; D010587:Phagocytosis; D020011:Protective Agents / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000172:deficiency / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000378:metabolism* / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000201:enzymology / Q000502:physiology*; D013666:Tears / Q000378:metabolism
chemical_list: D020011:Protective Agents; D037663:Pulmonary Surfactant-Associated Protein D; D057056:Cysteine Proteases