title: Human suppressive neutrophils CD16bright/CD62Ldim exhibit decreased adhesion.
abstract: Neutrophils are essential effector cells in host defense against invading pathogens. Regulation of adhesion, migration, and chemotactic processes is important in the homing and activation of these cells. We recently described three distinct subsets of circulating human neutrophils in peripheral blood during acute systemic inflammation. One subset, CD16(bright)/CD62L(dim), has immune suppressive characteristics because it can inhibit T-cell proliferation. The other two subsets consist of banded CD16(dim)/CD62L(bright) and phenotypically mature (normal) CD16(bright)/CD62L(bright) neutrophils. The current study was designed to determine the adhesion characteristics of these different neutrophil subsets. Analysis of adhesion to activated endothelium under flow conditions revealed that CD16(bright)/CD62L(dim) neutrophils adhered less compared with CD16(bright)/CD62L(bright) and CD16(dim)/CD62L(bright) neutrophils. This decrease in binding capacity could be mimicked in the other neutrophil subsets by blocking L-selectin. Chemotaxis of CD16(bright)/CD62L(dim) neutrophils to the end-target chemoattractant N-formylmethionine-leucine-phenylalanine was lower compared with that for the CD16(dim)/CD62L(bright) neutrophil subset, whereas chemotaxis to cell-derived chemoattractant CXCL8 was comparable. Our data indicate that capture on endothelium under flow conditions, a key mechanism necessary for extravasation, of CD16(bright)/CD62L(dim) neutrophils to inflammatory sites is attenuated, which may facilitate migration of these cells to other tissue localizations. Modulation of this process is a potential target to manipulate inflammation because potentiation of this immune suppression might aid in anti-inflammatory therapy.
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Vera M
authors.initials: VM
authors.lastname: Kamp
authors.forename: Janesh
authors.initials: J
authors.lastname: Pillay
authors.forename: Jan-Willem J
authors.initials: JW
authors.lastname: Lammers
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
authors.forename: Laurien H
authors.initials: LH
authors.lastname: Ulfman
authors.forename: Leo
authors.initials: L
authors.lastname: Koenderman
mesh_terms: D002448:Cell Adhesion / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007154:Immune System Diseases / Q000378:metabolism*; D019041:L-Selectin / Q000096:biosynthesis*; D007960:Leukocyte Disorders / Q000378:metabolism*; D036904:Leukocyte Rolling / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D017452:Receptors, IgG / Q000096:biosynthesis*
chemical_list: D017452:Receptors, IgG; D019041:L-Selectin