Regulation of corneal inflammation by neutrophil‐dependent cleavage of keratan sulfate proteoglycans as a model for breakdown of the chemokine gradient

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: keratitis;    extracellular matrix;    matrix metalloproteinase;   

DOI  :  10.1189/jlb.0310134

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Keratocanandlumicanaresmall,leucine‐richrepeatKSPGsintheextracellularmatrix(ECM)ofthemammaliancornea,whoseprimaryroleistomaintaincornealtransparency.Inthecurrentstudy,weexaminedtheroleoftheseproteoglycansinthebreakdownofthechemokinegradientandresolutionofcornealinflammation.LPSwasinjectedintothecornealstromaofC57BL/6mice,andcornealextractswereexaminedbyimmunoblotanalysis.Wefoundreducedexpressionofthe52‐kDkeratocanproteinafter6handconversely,increasedexpressionof34/37kDimmunoreactiveproducts.Further,appearanceofthe34/37‐kDproteinswasdependentonneutrophilinfiltrationtothecornea,astheappearanceoftheseproductswascoincidentwithneutrophilinfiltration,andthe34/37‐kDproductswerenotdetectedinexplantedcorneasorinCXCR2−/−corneaswithdeficientneutrophilrecruitment.Furthermore,the34/37‐kDproductsandCXCL1/KCweredetectedintheanteriorchamber,intowhichthecornealstromadrains;andCXCL1/KCwaselevatedsignificantlyinkeratocan−/−andlumican−/−mice.Together,thesefindingsindicatethattheinflammatoryresponseinthecorneaisregulatedbyproteoglycan/CXCL1complexes,andtheirdiffusionintotheanteriorchamberisconsistentwithreleaseofachemokinegradientandresolutionofinflammation...

【 授权许可】

CC BY