Apoptotic neutrophils are phagocytosed by fibroblasts with participation of the fibroblast vitronectin receptor and involvement of a mannose/fucose-specific lectin.
The fate of neutrophils (PMNs) at sites of inflammation is important to our understanding of many disease processes. Previously, it had been widely assumed that extravasated PMNs inevitably disintegrated before their fragments were removed by local phagocytes, but we have recently described an alternative process whereby senescent PMNs undergo apoptosis (programmed cell death). This process leads to macrophage (Mphi) ingestion of the intact cell by a novel phagocytic recognition process. In this study, we show that monolayers of fibroblasts also can selectively phagocytose apoptotic PMNs and that the recognition of apoptotic PMNs by fibroblasts involves two distinct mechanisms: one uses the vitronectin receptor, as in Mphi ingestion of PMNs; the other uses a mannose/fucose-specific lectin, which plays no part in Mphi phagocytosis of apoptotic PMNs. The direct interactions between PMNs and fibroblasts demonstrated herein may have implications for our understanding of the relationship between inflammation and scarring in many diseases.
Hall
S E
SE
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Savill
J S
JS
Henson
P M
PM
Haslett
C
C
D000595:Amino Acid Sequence; D017209:Apoptosis; D002413:Cations, Divalent / Q000494:pharmacology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000502:physiology*; D005643:Fucose / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000502:physiology*; D037102:Lectins / Q000502:physiology*; D008358:Mannose / Q000494:pharmacology; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology*; D009842:Oligopeptides; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D010587:Phagocytosis; D011134:Polysaccharides / Q000494:pharmacology; D016024:Receptors, Cytoadhesin / Q000502:physiology*; D019030:Receptors, Vitronectin; D014018:Tissue Distribution
D002413:Cations, Divalent; D016023:Integrins; D037102:Lectins; D009842:Oligopeptides; D010455:Peptides; D011134:Polysaccharides; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin; D005643:Fucose; C047981:arginyl-glycyl-aspartic acid; C007789:fucoidan; D008358:Mannose