MACROPHAGE RECEPTORS FOR LUMICAN - A CORNEAL KERATAN SULFATE PROTEOGLYCAN

Purpose. Keratan sulfate proteoglycans (KSPGs) of the cornea exhibit a characteristic change in glycosylation resulting from stromal inflamm ation and scarring. To examine potential roles for these molecules in the pathobiology of the cornea, the authors investigated interaction o f inflammatory macrophages with KSPGs in vitro. Methods. Attachment an d spreading of mouse peritoneal macrophages were examined on surfaces coated with corneal proteoglycans, intact or with modified glycosylati on. Solution-phase interactions were demonstrated using soluble proteo glycans labeled with I-125-Iodine or with fluorescein. The affinity an d specificity of these interactions were determined by competitive inh ibition with unlabeled proteoglycans. Results. Macrophages did not adh ere to intact corneal KSPGs but did attach and spread rapidly on the l umican core protein after the removal of keratan sulfate chains. Arter ial lumican, a nonsulfated form of this proteoglycan, also stimulated macrophage attachment. Labeled arterial lumican specifically bound to macrophages with high affinity. Flow cytometry demonstrated a high pro portion of macrophages binding lumican. Lumican binding was inhibited by divalent cation-chelators and by polyanions. Inhibition and kinetic s of lumican binding were distinct from interaction of macrophages wit h maleated bovine serum albumin, collagen, laminin, and fibronectin. C onclusions. The highly sulfated KSPGs of cornea do not promote macroph age adhesion; however, the low-sulfate lumican present in pathologic c orneas may act to localize macrophages in regions of inflammation. The lumican receptor differs from macrophage scavenger receptors and from receptors for several other extracellular matrix molecules.