Chemotactic activity of soluble Fas ligand against phagocytes.
A recombinant soluble form of human Fas ligand (sFasL) was tested for its chemotactic activity against human and mouse polymorphonuclear neutrophils (PMN) by the Boyden chamber method. sFasL exhibited a potent chemotactic activity against both human and mouse PMN and HL-60 cells when differentiated into neutrophils or monocytes. A neutralizing anti-FasL mAb abolished the chemotactic activity, while control mAb did not. Ligation of Fas by either IgM- or IgG-type anti-Fas mAb also induced PMN migration. PMN derived from lpr mice that express few Fas molecules did not respond to sFasL. In contrast, those derived from lpr(cg) mice that express Fas molecules with a mutated death domain normally responded to sFasL chemotaxis. These results directly indicated a chemotactic activity of sFasL against PMN and suggest a novel signaling function of Fas, which appears to be independent of the death domain-mediated apoptosis.
Seino
K
K
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan. mo97g074@md.tsukuba.ac.jp
Iwabuchi
K
K
Kayagaki
N
N
Miyata
R
R
Nagaoka
I
I
Matsuzawa
A
A
Fukao
K
K
Yagita
H
H
Okumura
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D053222:Fas Ligand Protein; D018922:HL-60 Cells; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr; D009154:Mutation; D009504:Neutrophils / Q000187:drug effects*; D010586:Phagocytes / Q000187:drug effects*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D019014:fas Receptor / Q000737:chemistry / Q000235:genetics
D000911:Antibodies, Monoclonal; D002630:Chemotactic Factors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D019014:fas Receptor