title: The role for decorin in delayed-type hypersensitivity.
abstract: Decorin, a small leucine-rich proteoglycan, regulates extracellular matrix organization, growth factor-mediated signaling, and cell growth. Because decorin may directly modulate immune responses, we investigated its role in a mouse model of contact allergy (oxazolone-mediated delayed-type hypersensitivity [DTH]) in decorin-deficient (Dcn(-/-)) and wild-type mice. Dcn(-/-) mice showed a reduced ear swelling 24 h after oxazolone treatment with a concurrent attenuation of leukocyte infiltration. These findings were corroborated by reduced glucose metabolism, as determined by (18)fluordeoxyglucose uptake in positron emission tomography scans. Unexpectedly, polymorphonuclear leukocyte numbers in Dcn(-/-) blood vessels were significantly increased and accompanied by large numbers of flattened leukocytes adherent to the endothelium. Intravital microscopy and flow chamber and static adhesion assays confirmed increased adhesion and reduced transmigration of Dcn(-/-) leukocytes. Circulating blood neutrophil numbers were significantly increased in Dcn(-/-) mice 24 h after DTH elicitation, but they were only moderately increased in wild-type mice. Expression of the proinflammatory cytokine TNF-α was reduced, whereas syndecan-1 and ICAM-1 were overexpressed in inflamed ears of Dcn(-/-) mice, indicating that these adhesion molecules could be responsible for increased leukocyte adhesion. Decorin treatment of endothelial cells increased tyrosine phosphorylation and reduced syndecan-1 expression. Notably, absence of syndecan-1 in a genetic background lacking decorin rescued the attenuated DTH phenotype of Dcn(-/-) mice. Collectively, these results implicated a role for decorin in mediating DTH responses by influencing polymorphonuclear leukocyte attachment to the endothelium. This occurs via two nonmutually exclusive mechanisms that involve a direct antiadhesive effect on polymorphonuclear leukocytes and a negative regulation of ICAM-1 and syndecan-1 expression.
authors: Institute of Physiological Chemistry and Pathobiochemistry, D-48149 Münster, Germany. dgseidle@uni-muenster.de
authors: Daniela G
authors: DG
authors: Seidler
authors: Negia A
authors: NA
authors: Mohamed
authors: Carla
authors: C
authors: Bocian
authors: Anika
authors: A
authors: Stadtmann
authors: Sven
authors: S
authors: Hermann
authors: Klaus
authors: K
authors: Schäfers
authors: Michael
authors: M
authors: Schäfers
authors: Renato V
authors: RV
authors: Iozzo
authors: Alexander
authors: A
authors: Zarbock
authors: Martin
authors: M
authors: Götte
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D058575:Decorin / Q000276:immunology* / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D049268:Positron-Emission Tomography; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053668:Syndecan-1 / Q000096:biosynthesis / Q000276:immunology; D014057:Tomography, X-Ray Computed
chemical_list: C546879:Dcn protein, mouse; D058575:Decorin; D053668:Syndecan-1; D018799:Intercellular Adhesion Molecule-1