Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HSV-1 induced stromal keratitis (HSK) is an immune-mediated disease. The role of macrophages in this process is still unclear. In this study we investigated the influence of specific macrophage depletion from the spleen and the submandibular lymph nodes by dichloromethylene diphosphonate liposomes (Cl(2)MDP-LIP) on the course of HSV-1 keratitis. BALB/c mice were infected corneally with 10(5)PFU of HSV-1 (KOS). Groups of mice received Cl(2)MDP-LIP 7 and 2 days prior to infection. Cl(2)MDP-LIP were given by various routes: intravenously (i.v.) for macrophage depletion in the spleen; subcutaneously for macrophage depletion in the submandibular regional lymph node (s.c.); or both i.v. and s.c. The development of HSV-1 keratitis was evaluated clinically and histologically. A standard plaque assay from the infected eyes was used to measure virus clearance. Seventy-nine percent of the HSV-1-infected control mice (n = 14) developed severe stromal keratitis by day 14 p.i. The development of stromal keratitis was inhibited by Cl(2)MDP-LIP given s.c. (64%;n = 14;P < 0.05), i.v. and s.c. (50%;n = 14;P < 0.05), but not by i.v. treatment alone (77%;n = 13). After s.c., i.v. and s.c. Cl(2)MDP-LIP injection, histologically the corneal stroma had a decrease in inflammatory cell infiltration by day 14 p.i. compared to the control group, and the DTH response was reduced. The healing of epithelial HSV-1 keratitis and the virus clearance were not affected significantly. These results indicate an important function of macrophages in the course of HSV-1 keratitis. Virus replication in the eye does not appear to be affected by monocytes/macrophages of lymph nodes and spleen. In contrast, the immunopathological process of stromal HSV-keratitis that results in corneal destruction is profoundly accelerated by macrophages in the lymph nodes.
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PMID:Incidence and severity of herpetic stromal keratitis: impaired by the depletion of lymph node macrophages. 1118 Sep 75

Necrotizing herpetic stromal keratitis (HSK) in mice rapidly improved after amniotic membrane transplantation (AMT). In this study we determined the fate of polymorphonuclear neutrophils (PMN) after AMT. AMT or tarsorrhaphy (T) was performed in BALB/c mice with ulcerative HSK. After 2 days, corneas were studied histologically and by transmission electron microscopy (TEM). CD11b, Gr-1, and TUNEL-positive cells were identified. Macrophages were depleted by subconjunctival injection of dichloromethylene-diphosphonate-liposomes (Cl(2)MDP-LIP) before AMT. Corneas were studied for interleukin (IL)-1alpha, IL-2, interferon (IFN)-gamma, CXCL1, CXCL2, and tumor necrosis factor (TNF)-alpha production by ELISA. PMN-enriched cell preparations co-cultured with amniotic membrane (AM) or with AM and such recombinant (r) cytokines as rIL-1alpha, rIL-2, and rTNF-alpha or supernatants from activated lymphocytes were investigated by flow cytometry (Annexin-V/7-AAD and TUNEL), and a dimethylthiazolyl-diphenyltetrazolium-bromide (MTT)-viability assay. Corneas in the AMT mice had less inflammation, fewer PMN-like cells and fewer CD11b+, and Gr-1+ cells (P<0.01), but a higher ratio of apoptotic to viable PMN-resembling cells (P<0.01) than the T mice. Phagocytic removal of apoptotic PMN-like cells by macrophages was evident in the AMT group. After Cl(2)MDP-LIP treatment, the corneas had more cell debris and apoptotic cells with PMN-like morphology. The concentrations of IL-1alpha, IL-2, CXCL1, and TNF-alpha were reduced in corneas of the AMT group as compared to that of the T group, while the concentration of CXCL2 was increased. Apoptosis of PMN-resembling cells was detected following cocultivation with AM, even when proinflammatory cytokines were present. Resolution of corneal inflammation in mice with necrotizing HSK after AMT is associated with increased apoptosis of PMN-like cells, reduction of pro-inflammatory cytokines, an increase of CXCL2, and increased removal of apoptotic PMN-like cells by macrophages.
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PMID:On the influence of neutrophils in corneas with necrotizing HSV-1 keratitis following amniotic membrane transplantation. 1763 63