Monoclonal IgA Antibodies Protect Against Acanthamoeba Keratitis

Leher, Henry; Zaragoza, Fernando; Taherzadeh, Sherine; Alizadeh, Hassan; Niederkorn, Jérry Y.

doi:10.1006/exer.1999.0678

Cited by 52 publications

(17 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Orally immunized Chinese hamsters have been shown to produce significantly high levels of IgA antibody that can be readily detected in both tear secretions and enteric washes (14). Since the tears continuously bathe the ocular surface, the anti-MIP-133 IgA antibodies have direct and prolonged contact with trophozoites and their products.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pathogenic Acanthamoeba spp. Secrete a Mannose-Induced Cytolytic Protein That Correlates with the Ability To Cause Disease

et al. 2003

Self Cite

View full text Add to dashboard Cite

The pathogenesis of Acanthamoeba keratitis begins when Acanthamoeba trophozoites bind specifically to mannosylated glycoproteins upregulated on the surfaces of traumatized corneal epithelial cells. When Acanthamoeba castellanii trophozoites are grown in methyl-␣-D-mannopyranoside, they are induced to secrete a novel 133-kDa protein that is cytolytic to corneal epithelial cells. Clinical isolates of Acanthamoeba spp., and not the soil isolates, were proficient at producing a mannose-induced protein (MIP-133) and generating disease in Chinese hamsters. The purified protein was efficient at killing corneal epithelial cells, the first mechanistic barrier, by inducing apoptosis in a caspase 3-dependent pathway. Subsequent steps in pathogenesis require the amoebae to penetrate and degrade collagen. Only the clinical isolates tested were efficient at migrating through a collagenous matrix in vitro, presumably by MIP-133 degradation of both human type I and human type IV collagen. A chicken anti-MIP-133 antiserum effectively bound to the protein and blocked collagenolytic activity, migration, and cytopathic effects (CPE) against corneal cells in vitro. Chinese hamsters orally immunized with MIP-133 displayed a >30% reduction in disease. Immunoglobulin A isolated from immunized animals bound MIP-133 and blocked CPE on corneal cells in vitro. Animals induced to generate severe chronic infections displayed significant reductions in disease symptoms upon oral immunization postinfection. These data suggest that MIP-133 production might be necessary to initiate corneal disease and that it may play an important role in the subsequent steps of the pathogenic cascade of Acanthamoeba keratitis. Furthermore, as antibodies produced both prior to and after infection reduced clinical symptoms of disease, the protein may represent an important immunotherapeutic target for Acanthamoeba keratitis.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Enteric washes were collected as stated previously (14). Briefly, the enteric washes were collected from Chinese hamsters after the animals were anesthetized with ketamine and euthanized by cervical dislocation.…”

Section: Animalsmentioning

confidence: 99%

Pathogenic Acanthamoeba spp. Secrete a Mannose-Induced Cytolytic Protein That Correlates with the Ability To Cause Disease

et al. 2003

Self Cite

View full text Add to dashboard Cite

show abstract

“…(1) binding of the trophozoites to the corneal epithelial cells via lectin-glycoprotein interactions (Leher et al, 1999;Morton et al, 1991;Panjwani et al, 1990;Panjwani et al, 1992), (2) generation of cytopathic factors that destroy the corneal epithelium and stromal cells (Cao et al, 1998;Leher et al, 1998), (3) production of proteolytic enzymes that facilitate the invasion and penetration of trophozoites through the basement membrane and stroma (Cao et al, 1998;Hadas & Mazur, 1993;Mitra et al, 1995;Mitro et al, 1994), (4) elaboration of collagenolytic enzymes that degrade types I and IV collagens, which constitute the corneal matrix (Badenoch et al, 1990;Mitro et al, 1994) We have shown that trophozoites exposed to free mannose for 48 hr or longer are induced to release a soluble 133-kDa cytolytic factor (MIP-133) that mediates contact-independent cytolysis of corneal epithelial cells in vitro (Leher et al, 1998). Therefore, the parasite's binding to the mannose receptors induces the generation of cytopathic factors that destroy the corneal epithelial and stromal cells and is an important step in the pathogenicity of Acanthamoeba keratitis.…”

Section: Introductionmentioning

confidence: 99%

Modulation of corneal and stromal matrix metalloproteinase by the mannose-induced Acanthamoeba cytolytic protein

Alizadeh

Neelam

et al. 2008

Experimental Eye Research

Self Cite

View full text Add to dashboard Cite

The involvement of the mannose-induced Acanthamoeba cytopathic protein in tissue injury and activation of metalloproteinase of corneal and stromal cells was examined in vitro.Activation of MMP-1, MMP-2, MMP-3, and MMP-9 induced by MIP-133 on human corneal epithelial and stromal cell cultures was examined by reverse transcriptase polymerase chain reaction (RT-PCR), and ELISA.MMP-1, MMP-2, MMP-3, and MMP-9 mRNA were expressed in both cultured human corneal epithelial and stromal cells. When the epithelial cells were exposed to MIP-133 protein, the mRNA expression for MMP-1 and MMP-9 was unchanged. However, the transcript for MMP-2 and MMP-3 was decreased by two fold. By contrast, the expression of MMP-2 and MMP-3 was significantly upregulated The results indicate that the MIP-133 protein modulates MMP-2 and-3 expression differently in human corneal epithelial and stromal cells.

show abstract

“…For example, 10 mg/ml chondroitin sulfate could inhibit spore adherence on the corneal surface by 36%, but it did not show any inhibitory effects in the corneal epithelium monolayer model. For the in vivo animal model, the influencing factors for the investigations of fungal adherence on the corneal surface are too complicated since the involvement of tear ingredients and blinking [34][35][36][37][38][39][40]. Furthermore, the construction of animal models of fungal keratitis requires a longer amount of time than that required for spore adherence.…”

Section: Discussionmentioning

confidence: 99%