title: Exocytosis acts as a modulator of the ILT4-mediated inhibition of neutrophil functions.
abstract: Neutrophils play a major role in inflammatory responses and immune defense against pathogens. Even though expression of inhibitory receptors has been reported on neutrophils, their role remains poorly defined. Here we show that primary human neutrophils expressed immunoglobulin-like transcript 4 (ILT4) inhibitory receptor and that this expression was induced during differentiation of the myelomonoblast PLB-985 cell line into "neutrophil-like" cells. Functional assays indicated that human leukocyte antigen G, the preferred ligand of ILT4, inhibited the phagocytic function of neutrophils. ILT4 engagement also impaired reactive oxygen species production induced through CD32a and both receptors were found colocalized into neutrophil lipid rafts. Moreover, neutrophil degranulation induced through inflammatory stimuli increased ILT4 expression as a result of the rapid translocation of an intracellular pool to the cell surface. Consequently to this ILT4 up-regulation, the human leukocyte antigen G-mediated inhibition of neutrophil phagocytic function was enhanced. Finally, we found that ILT4 up-regulation induced on healthy donor neutrophils following stimulation was impaired in presence of plasma from patients with sepsis. Similarly, ILT4 up-regulation was inhibited in neutrophils from septic patients. Altogether, our results reveal a unique mechanism of regulation of neutrophil functions through ILT4 and its exocytosis that may have implications in inflammatory disorders.
authors.affiliation: Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institute of Emerging Diseases and Innovative Therapies, Service de Recherches en Hemato-Immunologie, Hopital St. Louis, 75475 Paris Cedex 10, France.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Baudhuin
authors.forename: Julie
authors.initials: J
authors.lastname: Migraine
authors.forename: Valerie
authors.initials: V
authors.lastname: Faivre
authors.forename: Laure
authors.initials: L
authors.lastname: Loumagne
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Lukaszewicz
authors.forename: Didier
authors.initials: D
authors.lastname: Payen
authors.forename: Benoit
authors.initials: B
authors.lastname: Favier
mesh_terms: D017209:Apoptosis; D005089:Exocytosis / Q000276:immunology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology*; D018613:Microscopy, Confocal; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology*; D016897:Respiratory Burst / Q000276:immunology*; D018805:Sepsis / Q000276:immunology / Q000378:metabolism
chemical_list: C491341:LILRB2 protein, human; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D011971:Receptors, Immunologic
keywords: HLA-G; LILRB2; granulocytes; inflammation