Gelatinase B in Vernal Keratoconjunctivitis

Abstract

To investigate the expression of gelatinase B in the conjunctiva of patients with vernal keratoconjunctivitis (VKC) and the cellular source of this enzyme. Methods: Conjunctival biopsy specimens from 12 patients with active VKC and 12 control subjects were studied using immunohistochemical techniques and a monoclonal antibody against gelatinase B. The phenotype of gelatinase B + inflammatory cells was examined using double immunohistochemical analysis and monoclonal antibodies against eosinophil peroxidase or macrophage CD68. Quantitative zymography was used to compare the activity of gelatinase B in conjunctival biopsy specimens from 10 patients with active VKC and 7 control subjects. Results: Gelatinase B was detected in a few polymorphonuclear cells in 8 control specimens. All VKC specimens showed gelatinase B immunoreactivity in the epi-thelial and stromal inflammatory infiltrate. Compared with control specimens, VKC specimens showed significantly more gelatinase B-positive cells (mean ± SD, 40.8±29.9 vs 10.3±2.4; PϽ.02). Most gelatinase B-positive cells were eosinophils (90.2%±3.6%). Zymography revealed that gelatinase B levels in VKC specimens were significantly higher than the levels found in normal conjunctiva (3780.3±3541.0 vs 610.1±397.1 scanning units; PϽ.03). Conclusions: These findings suggest overexpression of gelatinase B by eosinophils in VKC specimens and participation of gelatinase B in the pathologic changes in VKC. Clinical Relevance: Control of the release and/or activation of gelatinase B in eosinophils may provide a new therapeutic strategy for treating VKC.

Immuno-histochemical evaluation of conjunctival remodelling in vernal keratoconjunctivitis

“…In a previous study, we demonstrated a significant increased expression of gelatinase B in the conjunctiva from patients with VKC. 22 In conclusion, these results indicate that chronic inflammation in VKC is associated with increased deposition of tenascin and laminin that may reflect remodelling of the conjunctiva. The adhesive properties of tenascin and laminin may offer a relevant explanation for the mechanism by which inflammatory cells transmigrate into conjunctiva of patients with VKC.…”

Immuno-histochemical evaluation of conjunctival remodelling in vernal keratoconjunctivitis

“…In a previous study, we demonstrated a significant increased expression of gelatinase B in the conjunctiva from patients with VKC. 22 In conclusion, these results indicate that chronic inflammation in VKC is associated with increased deposition of tenascin and laminin that may reflect remodelling of the conjunctiva. The adhesive properties of tenascin and laminin may offer a relevant explanation for the mechanism by which inflammatory cells transmigrate into conjunctiva of patients with VKC.…”

IgE and eosinophil cationic protein (ECP) as markers of severity in the diagnosis of atopic keratoconjunctivitis

“…The subjects with corneal epithelial damage consistently exhibited the highest tear ECP measurements compared with normal subjects. In these cases, eosinophil products such as major basic protein and ECP may cause cellular disaggregation, epithelial desquamation and toxicity leading to corneal epitheliopathy and ulceration 22 23…”

Matrix metalloproteases in vernal keratoconjunctivitis, nasal polyps and allergic asthma

“…This lack of a positive correlation may be due to the fact that cell migration and anchorage is under the control of many chemotactic and ‘adhesive’ factors influencing cell residence in the stroma of inflamed tissues or simply to the relatively low number of patients studied. It has been previously shown that MMP‐9 can be produced by many inflammatory cells, such as macrophages, neutrophils, mast cells, eosinophils [16–19], T lymphocytes [26, 29] and monocytes [30].…”

Immuno-histochemical evaluation of conjunctival remodelling in vernal keratoconjunctivitis

“…In a previous study, we demonstrated a significant increased expression of gelatinase B in the conjunctiva from patients with VKC. 22 In conclusion, these results indicate that chronic inflammation in VKC is associated with increased deposition of tenascin and laminin that may reflect remodelling of the conjunctiva. The adhesive properties of tenascin and laminin may offer a relevant explanation for the mechanism by which inflammatory cells transmigrate into conjunctiva of patients with VKC.…”

IgE and eosinophil cationic protein (ECP) as markers of severity in the diagnosis of atopic keratoconjunctivitis

“…The subjects with corneal epithelial damage consistently exhibited the highest tear ECP measurements compared with normal subjects. In these cases, eosinophil products such as major basic protein and ECP may cause cellular disaggregation, epithelial desquamation and toxicity leading to corneal epitheliopathy and ulceration 22 23…”

Matrix metalloproteases in vernal keratoconjunctivitis, nasal polyps and allergic asthma

“…This lack of a positive correlation may be due to the fact that cell migration and anchorage is under the control of many chemotactic and ‘adhesive’ factors influencing cell residence in the stroma of inflamed tissues or simply to the relatively low number of patients studied. It has been previously shown that MMP‐9 can be produced by many inflammatory cells, such as macrophages, neutrophils, mast cells, eosinophils [16–19], T lymphocytes [26, 29] and monocytes [30].…”

Immuno-histochemical evaluation of conjunctival remodelling in vernal keratoconjunctivitis

“…In a previous study, we demonstrated a significant increased expression of gelatinase B in the conjunctiva from patients with VKC. 22 In conclusion, these results indicate that chronic inflammation in VKC is associated with increased deposition of tenascin and laminin that may reflect remodelling of the conjunctiva. The adhesive properties of tenascin and laminin may offer a relevant explanation for the mechanism by which inflammatory cells transmigrate into conjunctiva of patients with VKC.…”

IgE and eosinophil cationic protein (ECP) as markers of severity in the diagnosis of atopic keratoconjunctivitis

“…The subjects with corneal epithelial damage consistently exhibited the highest tear ECP measurements compared with normal subjects. In these cases, eosinophil products such as major basic protein and ECP may cause cellular disaggregation, epithelial desquamation and toxicity leading to corneal epitheliopathy and ulceration 22 23…”

Matrix metalloproteases in vernal keratoconjunctivitis, nasal polyps and allergic asthma

“…This lack of a positive correlation may be due to the fact that cell migration and anchorage is under the control of many chemotactic and ‘adhesive’ factors influencing cell residence in the stroma of inflamed tissues or simply to the relatively low number of patients studied. It has been previously shown that MMP‐9 can be produced by many inflammatory cells, such as macrophages, neutrophils, mast cells, eosinophils [16–19], T lymphocytes [26, 29] and monocytes [30].…”