Uptake of proteinase-α-macroglobulin complexes by macrophages☆

Debanne, Maria T.; Bell, Rosalind; Dolovich, J.

doi:10.1016/0304-4165(75)90309-8

Cited by 127 publications

(47 citation statements)

References 20 publications

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“…Our studies provide the first evidence that secretion of complement components by M~ plays a direct role in regulating M~ recognition and effector functions. Similar feedback mechanisms could link other M~ secretory and endocytic pathways, e.g., via intermediates such as a2-macroglobulin (41,42).…”

Section: Discussionmentioning

confidence: 96%

Local opsonization by secreted macrophage complement components. Role of receptors for complement in uptake of zymosan.

Ezekowitz¹,

Sim²,

Hill³

et al. 1984

The Journal of Experimental Medicine

189

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Circulating monocytes and tissue macrophages (Me) 1 secrete complement proteins and have distinct receptors for some of these secreted products. Although hepatocytes and possibly epithelial cells are major sources of plasma complement (1), Mcl synthesize C1 subcomponents (2, 3), C4 (4, 5), C2 (5-7) C5 (8), C3 (2, 8) and all the components of the alternative pathway and its control proteins (8). Current evidence indicates that M~ bear at least two distinct receptors for fragments of activated C3 (9, 10). The type one complement receptor, CR1 (205 kD) displays specificity for activated C3 (C3b) (11) and C4 (C4b) (12). CR 1 interacts with iC3b, the product of C3b cleavage by factor I (9), although anti-CR 1 antibodies that block C3b-dependent rosetting do not block iC3b-dependent rosetting (13,14). The type three complement receptor, CR3, (170 and 95 kD) interacts with iC3b, and possibly with the further degradation product C3dg (9).In order to investigate the physiological role of M¢ complement products we made use of monoclonal antibodies (ab) that are specific for CR1 (13) and that recognize epitopes associated with CR3 (15, 16). We found that deposition of M~-derived C3 on the acceptor surface of zymosan particles mediated binding and ingestion of zymosan via M~ CR3. Zymosan uptake could also be mediated via mannosyl, fucosyl receptors (MFR, 17) in those M~ populations that possess both CR3 and MFR activity (18). These studies indicate a role for M~ complement in local opsonization and host defense. Materials and Methods AnimalsSwiss outbred (PO) and CBAT6T6 and C57bl mice were bred at the Sir William Dunn School of Pathology, Oxford, and both sexes used at 20-30 g.

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Section: Discussionmentioning

confidence: 96%

Local opsonization by secreted macrophage complement components. Role of receptors for complement in uptake of zymosan.

Ezekowitz¹,

Sim²,

Hill³

et al. 1984

The Journal of Experimental Medicine

189

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“…Nonspecific binding of labeled proteins was estimated for each experiment, using washed erythrocytes (16). Nonspecific binding was 3 4 % at 37"C, and a negligible increase in binding was observed with time.…”

Section: Radiolabeling Of Proteinsmentioning

confidence: 99%

Receptor‐mediated binding of leukocyte elastase by chondrocytes

Bartholomew

Lowther

1987

Arthritis & Rheumatism

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Studies on the effect of leukocyte elastase on the metaboliSm of chondrocytes in culture have demonstrated that these cells possess a specific cell surface receptor for leukocyte-derived elastase. Purified elastase from rabbit and human leukocytes is capable of modulating the metabolism of the cell by causing a marked decrease in both proteoglycan and protein biosynthesis. Addition of '251-labeled elastase to chondrocytes maintained in suspension culture has shown that binding occurs, and that it is saturable and is inhibited by the addition of unlabeled enzyme. We ascertained that the active site of the enzyme was necessary for binding to the chondrocyte, since phenylmethylsulfonyl fluoriib inactivated leukocyte elastase failed to bind. Pancreatic elastase had only a slight afiinity for the receptof, whereas trypsin and bovine serum albumin failed to bind to any significant extent. Autoradiographic studies and the use of inhibitors of endocytosis, such as dansyl cadaverine, confirmed that endocytosis of elastase was the secondary event after cell binding.The characteristic features of chronic inflammatory arthritis include the formation of an invasive pannus, the result of synovial cell proliferation cou-

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“…Thus, human neutrophil leukocyte elastase äs well äs a 2 -macroglobul· in-elastase complexes are pinocytosed and phagocytosed, respectively, by alveolar macrophages, suggesting that at least some of the elastase activity found in macrophages may be ingested rather than formed de novo (1)(2)(3)(4). A previous report from this laboratory presented evidence that bronchoalveolar lavage-derived human granulocytes accumulate appreciable amounts of a r proteinase inhibitor-elastase complexes during passage across the blood-air barrier (5).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Elastase and α1-Proteinase Inhibitor-Elastase Uptake by Polymorphonuclear Leukocytes and Evidence of an Elastase-Specific Receptor

Dwenger¹,

Tost²,

Holle³

1986

Clinical Chemistry and Laboratory Medicine

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Summary:Neither resting nor stimulated isolated human polymorphonuclear leukocytes did bind or ingest preformed complexes of a r prpteinase Inhibitor and unlabeled/ 125 I-labeled human leukocyte elastase. In contrast, granulocytes bound unlabeled/ 125 I-labeled elastase and the extent of binding was reduced in the presence of respirätory burst stimulators, such äs 4ß-phorbol 12ß-myristate 13a-acetate, E. coli endotoxin, and N^formyl-jL-methionyl-L-leucyl-L-phenylalanine. In association/dissociation and competition Inhibition experiments it was demonstrated that granulöcyte^-elastase binding was specific and saturable. From Scatchard and non-linear regression analysis there was evidence of a two-class receptor model with independent binding sites. Calculated by the non-linear regression method assuming a two-class receptor model the characteristics of the high affinity/low capacity binding site were K! = 216 ± 129 · l O 6 l · mol" 1 (x ± s; n = 3) and Rj = 1.38 ± 0.95 nmol · 1~* corresponding to 0.083 · 10 6 receptors per cell, whereäs the low affinity/ high capacity binding site had the characteristics K 2 = 0.50 ± 0.09 -10 6 l-mol^1 and R 2 = 237 ± 103 nmol · l" 1 corresponding to 14.3 + 6.2 -10 6 receptors per cell. ]Elastase-Bindung in Gegenwart der respiratory burst-Stimulantien 4ß-Phorbol-12ß-myristat-13a-acetat, E. co/rVEndotoxin und Formyl-methionyl-leucyl-phenylalanin erniedrigt ist. Aus Assoziations-/Dissoziationsund Kompetitions-Inhibitions-Experimenten geht hervor, daß die Granulocyten-Elastase-Bindung spezifisch und sättigbar ist. Scatchard-und nichtlineare Regressions-Analyse deuten auf ein zweiklassiges Modell unabhängiger Rezeptoren hin. Aus der nichtlinearen Regressionsanalyse ergeben sich unter Annahme eines zweiklassigen Rezeptormodelis die Bindungskonstanten Kj = 216 ± 129 · l O 6 1 · mol' 1 (x ± s; n = 3) und Rj = 1,38 ± 0,95 nmol · l" 1 entsprechend 0,083 · l O 6 Rezeptoren pro Zelle für die hochaffine/niedrigkapazitive Bindungsstelle, während die niedrigaffine/hochkapazitive Bindungsstelle die Konstanten K 2 = 0,50 ± 0,09 • 10 6 l -mol-1 Und R 2 « 237 ± 103 nmol · l^1 entsprechend 14,3 ± 6,2 · 10 6 Rezeptoren pro Granulocyt besitzt. Untersuchungen zur Elastase* und a,i~Proteinaseinhibitor-Elastase-Aufnahme polymorphkerniger Leukocyten und Nachweis eines Elastaserezeptor^Systems

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Uptake of proteinase-α-macroglobulin complexes by macrophages☆

Cited by 127 publications

References 20 publications

Local opsonization by secreted macrophage complement components. Role of receptors for complement in uptake of zymosan.

Local opsonization by secreted macrophage complement components. Role of receptors for complement in uptake of zymosan.

Receptor‐mediated binding of leukocyte elastase by chondrocytes

Evaluation of Elastase and α1-Proteinase Inhibitor-Elastase Uptake by Polymorphonuclear Leukocytes and Evidence of an Elastase-Specific Receptor

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