Macrophage receptors for lumican. A corneal keratan sulfate proteoglycan.
OBJECTIVE
Keratan sulfate proteoglycans (KSPGs) of the cornea exhibit a characteristic change in glycosylation resulting from stromal inflammation and scarring. To examine potential roles for these molecules in the pathobiology of the cornea, the authors investigated interaction of inflammatory macrophages with KSPGs in vitro.


METHODS
Attachment and spreading of mouse peritoneal macrophages were examined on surfaces coated with corneal proteoglycans, intact or with modified glycosylation. Solution-phase interactions were demonstrated using soluble proteoglycans labeled with 125I-Iodine or with fluorescein. The affinity and specificity of these interactions were determined by competitive inhibition with unlabeled proteoglycans.


RESULTS
Macrophages did not adhere to intact corneal KSPGs but did attach and spread rapidly on the lumican core protein after the removal of keratan sulfate chains. Arterial 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 proportion of macrophages binding lumican. Lumican binding was inhibited by divalent cation-chelators and by polyanions. Inhibition and kinetics of lumican binding were distinct from interaction of macrophages with maleated bovine serum albumin, collagen, laminin, and fibronectin.


CONCLUSIONS
The highly sulfated KSPGs of cornea do not promote macrophage adhesion; however, the low-sulfate lumican present in pathologic corneas 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.
Funderburgh
J L
JL
Division of Biology, Kansas State University, Manhattan 66506-4901, USA.
Mitschler
R R
RR
Funderburgh
M L
ML
Roth
M R
MR
Chapes
S K
SK
Conrad
G W
GW
D000818:Animals; D000838:Anions / Q000494:pharmacology; D001667:Binding, Competitive; D002417:Cattle; D002448:Cell Adhesion; D002614:Chelating Agents / Q000494:pharmacology; D011508:Chondroitin Sulfate Proteoglycans / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003315:Cornea / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D005434:Flow Cytometry; D019793:Fluorescein; D005452:Fluoresceins; D007632:Keratan Sulfate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071234:Lumican; D017737:Macrophages, Peritoneal / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D011956:Receptors, Cell Surface / Q000378:metabolism*
D000838:Anions; D002614:Chelating Agents; D011508:Chondroitin Sulfate Proteoglycans; D005452:Fluoresceins; C000604307:Lum protein, mouse; D000071234:Lumican; D011956:Receptors, Cell Surface; D007632:Keratan Sulfate; D004492:Edetic Acid; D019793:Fluorescein