Soluble P-selectin glycoprotein ligand 1 inhibits ocular inflammation in a murine model of allergy

Erich C. Strauss, Kirsten A. Larson, Ina Brenneise, C. Stephen Foster, Glenn R. Larsen, Nancy A Lee, James J. Lee

Research output: Contribution to journalArticle

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Abstract

PURPOSE. To assess the anti-inflammatory modality of a soluble extracellular form of P-selectin glycoprotein ligand 1 (sPSGL-1) in a mouse model of ocular allergic response METHODS. Potential anti-inflammatory effects of sPSGL-1 were investigated in SWR/J mice sensitized by topical application of short ragweed pollen to the nasal mucosa followed by a challenge of the ocular mucosa with the same allergen. Five experimental groups were included in these studies: A, mice neither sensitized nor challenged with pollen (control group 1); B, animals sensitized but not challenged (control group 2); C, animals not sensitized but challenged (control group 3); D, animals sensitized and challenged; and E, sensitized animals treated with sPSGL-1 before pollen challenge. All experimental groups were evaluated for gross morphologic ocular changes, and histologic assessments were made to determine the onset/progression of inflammatory reactions and to look for evidence of eosinophil infiltration. RESULTS. Mice sensitized and challenged with pollen developed clinical signs consistent with human allergic conjunctivitis. These signs correlate with histologic changes in the conjunctival epithelium and stroma (e.g., edema and extensive eosinophil infiltration). Moreover, the ocular changes also correlated with evidence of eosinophil degranulation. However sensitized and challenged mice concurrently treated with sPSGL-1 displayed no inflammatory ocular changes associated with a ragweed-induced type-1 hypersensitivity reaction. The lack of ocular changes included the absence of histologic late-phase inflammatory changes of the conjunctiva and a 97% reduction in the induced eosinophil infiltrate. CONCLUSIONS. The antagonistic intervention of cell-cell interactions through the blockade of selectin-dependent leukocyte adhesion may offer novel therapeutic strategies to modulate inflammatory responses. The potent inhibitory effects on eosinophil recruitment and late-phase inflammation suggest a role for sPSGL-1 in the treatment of ocular allergic diseases.

Original languageEnglish (US)
Pages (from-to)1336-1342
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume40
Issue number7
StatePublished - 1999

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Hypersensitivity
Eosinophils
Inflammation
Pollen
Control Groups
Anti-Inflammatory Agents
Allergic Conjunctivitis
Ambrosia
Immediate Hypersensitivity
Selectins
Eye Diseases
Nasal Mucosa
Conjunctiva
Cell Communication
Allergens
P-selectin ligand protein
Edema
Mucous Membrane
Leukocytes
Epithelium

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Strauss, E. C., Larson, K. A., Brenneise, I., Foster, C. S., Larsen, G. R., Lee, N. A., & Lee, J. J. (1999). Soluble P-selectin glycoprotein ligand 1 inhibits ocular inflammation in a murine model of allergy. Investigative Ophthalmology and Visual Science, 40(7), 1336-1342.

Soluble P-selectin glycoprotein ligand 1 inhibits ocular inflammation in a murine model of allergy. / Strauss, Erich C.; Larson, Kirsten A.; Brenneise, Ina; Foster, C. Stephen; Larsen, Glenn R.; Lee, Nancy A; Lee, James J.

In: Investigative Ophthalmology and Visual Science, Vol. 40, No. 7, 1999, p. 1336-1342.

Research output: Contribution to journalArticle

Strauss, EC, Larson, KA, Brenneise, I, Foster, CS, Larsen, GR, Lee, NA & Lee, JJ 1999, 'Soluble P-selectin glycoprotein ligand 1 inhibits ocular inflammation in a murine model of allergy', Investigative Ophthalmology and Visual Science, vol. 40, no. 7, pp. 1336-1342.
Strauss, Erich C. ; Larson, Kirsten A. ; Brenneise, Ina ; Foster, C. Stephen ; Larsen, Glenn R. ; Lee, Nancy A ; Lee, James J. / Soluble P-selectin glycoprotein ligand 1 inhibits ocular inflammation in a murine model of allergy. In: Investigative Ophthalmology and Visual Science. 1999 ; Vol. 40, No. 7. pp. 1336-1342.
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abstract = "PURPOSE. To assess the anti-inflammatory modality of a soluble extracellular form of P-selectin glycoprotein ligand 1 (sPSGL-1) in a mouse model of ocular allergic response METHODS. Potential anti-inflammatory effects of sPSGL-1 were investigated in SWR/J mice sensitized by topical application of short ragweed pollen to the nasal mucosa followed by a challenge of the ocular mucosa with the same allergen. Five experimental groups were included in these studies: A, mice neither sensitized nor challenged with pollen (control group 1); B, animals sensitized but not challenged (control group 2); C, animals not sensitized but challenged (control group 3); D, animals sensitized and challenged; and E, sensitized animals treated with sPSGL-1 before pollen challenge. All experimental groups were evaluated for gross morphologic ocular changes, and histologic assessments were made to determine the onset/progression of inflammatory reactions and to look for evidence of eosinophil infiltration. RESULTS. Mice sensitized and challenged with pollen developed clinical signs consistent with human allergic conjunctivitis. These signs correlate with histologic changes in the conjunctival epithelium and stroma (e.g., edema and extensive eosinophil infiltration). Moreover, the ocular changes also correlated with evidence of eosinophil degranulation. However sensitized and challenged mice concurrently treated with sPSGL-1 displayed no inflammatory ocular changes associated with a ragweed-induced type-1 hypersensitivity reaction. The lack of ocular changes included the absence of histologic late-phase inflammatory changes of the conjunctiva and a 97{\%} reduction in the induced eosinophil infiltrate. CONCLUSIONS. The antagonistic intervention of cell-cell interactions through the blockade of selectin-dependent leukocyte adhesion may offer novel therapeutic strategies to modulate inflammatory responses. The potent inhibitory effects on eosinophil recruitment and late-phase inflammation suggest a role for sPSGL-1 in the treatment of ocular allergic diseases.",
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N2 - PURPOSE. To assess the anti-inflammatory modality of a soluble extracellular form of P-selectin glycoprotein ligand 1 (sPSGL-1) in a mouse model of ocular allergic response METHODS. Potential anti-inflammatory effects of sPSGL-1 were investigated in SWR/J mice sensitized by topical application of short ragweed pollen to the nasal mucosa followed by a challenge of the ocular mucosa with the same allergen. Five experimental groups were included in these studies: A, mice neither sensitized nor challenged with pollen (control group 1); B, animals sensitized but not challenged (control group 2); C, animals not sensitized but challenged (control group 3); D, animals sensitized and challenged; and E, sensitized animals treated with sPSGL-1 before pollen challenge. All experimental groups were evaluated for gross morphologic ocular changes, and histologic assessments were made to determine the onset/progression of inflammatory reactions and to look for evidence of eosinophil infiltration. RESULTS. Mice sensitized and challenged with pollen developed clinical signs consistent with human allergic conjunctivitis. These signs correlate with histologic changes in the conjunctival epithelium and stroma (e.g., edema and extensive eosinophil infiltration). Moreover, the ocular changes also correlated with evidence of eosinophil degranulation. However sensitized and challenged mice concurrently treated with sPSGL-1 displayed no inflammatory ocular changes associated with a ragweed-induced type-1 hypersensitivity reaction. The lack of ocular changes included the absence of histologic late-phase inflammatory changes of the conjunctiva and a 97% reduction in the induced eosinophil infiltrate. CONCLUSIONS. The antagonistic intervention of cell-cell interactions through the blockade of selectin-dependent leukocyte adhesion may offer novel therapeutic strategies to modulate inflammatory responses. The potent inhibitory effects on eosinophil recruitment and late-phase inflammation suggest a role for sPSGL-1 in the treatment of ocular allergic diseases.

AB - PURPOSE. To assess the anti-inflammatory modality of a soluble extracellular form of P-selectin glycoprotein ligand 1 (sPSGL-1) in a mouse model of ocular allergic response METHODS. Potential anti-inflammatory effects of sPSGL-1 were investigated in SWR/J mice sensitized by topical application of short ragweed pollen to the nasal mucosa followed by a challenge of the ocular mucosa with the same allergen. Five experimental groups were included in these studies: A, mice neither sensitized nor challenged with pollen (control group 1); B, animals sensitized but not challenged (control group 2); C, animals not sensitized but challenged (control group 3); D, animals sensitized and challenged; and E, sensitized animals treated with sPSGL-1 before pollen challenge. All experimental groups were evaluated for gross morphologic ocular changes, and histologic assessments were made to determine the onset/progression of inflammatory reactions and to look for evidence of eosinophil infiltration. RESULTS. Mice sensitized and challenged with pollen developed clinical signs consistent with human allergic conjunctivitis. These signs correlate with histologic changes in the conjunctival epithelium and stroma (e.g., edema and extensive eosinophil infiltration). Moreover, the ocular changes also correlated with evidence of eosinophil degranulation. However sensitized and challenged mice concurrently treated with sPSGL-1 displayed no inflammatory ocular changes associated with a ragweed-induced type-1 hypersensitivity reaction. The lack of ocular changes included the absence of histologic late-phase inflammatory changes of the conjunctiva and a 97% reduction in the induced eosinophil infiltrate. CONCLUSIONS. The antagonistic intervention of cell-cell interactions through the blockade of selectin-dependent leukocyte adhesion may offer novel therapeutic strategies to modulate inflammatory responses. The potent inhibitory effects on eosinophil recruitment and late-phase inflammation suggest a role for sPSGL-1 in the treatment of ocular allergic diseases.

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