Human Thy-1 induces secretion of matrix metalloproteinase-9 and CXCL8 from human neutrophils.
Neutrophils are the first cells arriving at sites of acute inflammation. On their way from blood to the site of inflammation, neutrophils have to adhere to endothelial cells (EC), to transverse the basement membrane and subsequently to travel through the interstitial matrix. Recently, we have shown that human Thy-1 is an alternate EC receptor for the leukocyte integrin Mac-1 that contributes to leukocyte recruitment to sites of inflammation, providing a new pathway for adhesion and transmigration of neutrophils. Here, we studied the effect of Thy-1-mediated adhesion on neutrophil functions. Binding of neutrophils to recombinant human Thy-1 stimulated the release of MMP-9 from neutrophils, resulting in their enhanced migration through collagen-IV and matrigel. Further, we showed that neutrophil interaction with Thy-1 stimulated secretion of CXCL8 and thus could support the attraction of additional neutrophils to inflammatory sites. Blocking experiments confirmed the pivotal roles of Thy-1 on activated dermal EC or fibroblasts and its counter receptor CD18 on neutrophils for the regulation of MMP-9 and CXCL8 release from neutrophils. Our results support the general concept that the function of 'adhesion molecules' in particular of human Thy-1, may not only be to provide mechanical support but also regulate neutrophil functions.
Saalbach
Anja
A
Department of Dermatology, Venerology and Allergology, Medical Faculty of the Leipzig University, Leipzig, Germany. Anja.Saalbach@medizin.uni-leipzig.de
Arnhold
Jürgen
J
Lessig
Jacqueline
J
Simon
Jan C
JC
Anderegg
Ulf
U
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D018821:CD18 Antigens / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication; D054441:Cell Migration Assays, Leukocyte; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism*; D007518:Isoantibodies / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011565:Psoriasis / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000473:pathology; D018800:Thy-1 Antigens / Q000494:pharmacology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; C508606:CXCL8 protein, human; D017077:Culture Media, Conditioned; D016209:Interleukin-8; D007518:Isoantibodies; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D018800:Thy-1 Antigens; C035678:anti-Thy antibody; D020780:Matrix Metalloproteinase 9