Antileukoproteinase - Modulation of neutrophil function and therapeutic effects on anti-type II collagen antibody-induced arthritis
(2004) In Arthritis and Rheumatism 50(7). p.2347-2359- Abstract
- Objective. Antileukoproteinase (ALP) is a physiologic inhibitor of granulocytic serine proteases. The present study was undertaken to investigate its therapeutic benefit in an antibody-transfer model of erosive polyarthritis and to elucidate its potential to interfere with immune complex-dependent inflammatory pathways. Methods. Arthritis development was induced in male (BALB/c x B10.Q)F-1 mice by intravenous injection of two monoclonal antibodies specific for type II collagen and was quantified by clinical scoring and histopathology. Arthritis severity was assessed in a cohort of mice under systemic treatment with recombinant human ALP (daily doses of 0.1 mg for 5 days starting immediately after disease induction) in comparison with... (More)
- Objective. Antileukoproteinase (ALP) is a physiologic inhibitor of granulocytic serine proteases. The present study was undertaken to investigate its therapeutic benefit in an antibody-transfer model of erosive polyarthritis and to elucidate its potential to interfere with immune complex-dependent inflammatory pathways. Methods. Arthritis development was induced in male (BALB/c x B10.Q)F-1 mice by intravenous injection of two monoclonal antibodies specific for type II collagen and was quantified by clinical scoring and histopathology. Arthritis severity was assessed in a cohort of mice under systemic treatment with recombinant human ALP (daily doses of 0.1 mg for 5 days starting immediately after disease induction) in comparison with untreated controls. Concomitantly, functional assays (phagocytosis, oxidative burst, fluorescence-activated cell sorting analysis of integrin expression) were performed on neutrophils upon in vitro stimulation by IgG-coated latex beads. Results. ALP treatment reduced arthritis incidence and severity and had a protective effect against cartilage and bone erosion. ALP inhibited the conversion of the leukocyte beta2 integrins into an active conformation upon Fc receptor stimulation of granulocytes. ALP bound to the actin-bundling protein L-plastin and down-modulated filamentous actin assembly in response to stimulation with IgG-coated latex beads in granulocytes. ALP exerted additional inhibitory effects on neutrophil functions associated with cytoskeletal reorganization, such as phagocytosis and oxidative burst. Conclusion. In addition to its antiprotease activity, ALP exerts a variety of blocking effects on neutrophil functions, probably due to modulation of cytoskeletal changes, that may contribute to this inhibitor's antiarthritis potential and qualify it as a multifunctional regulator of inflammatory responses. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/272586
- author
- Sehnert, B ; Cavcic, A ; Bohm, B ; Kalden, JR ; Kutty Selva, Nandakumar LU ; Holmdahl, Rikard LU and Burkhardt, H
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Arthritis and Rheumatism
- volume
- 50
- issue
- 7
- pages
- 2347 - 2359
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000222820300037
- pmid:15248236
- scopus:3142684490
- pmid:15248236
- ISSN
- 1529-0131
- DOI
- 10.1002/art.20339
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019)
- id
- 667ef147-987e-4fff-b2ee-dd4a1930552f (old id 272586)
- date added to LUP
- 2016-04-01 12:12:07
- date last changed
- 2022-04-29 02:06:59
@article{667ef147-987e-4fff-b2ee-dd4a1930552f,
abstract = {{Objective. Antileukoproteinase (ALP) is a physiologic inhibitor of granulocytic serine proteases. The present study was undertaken to investigate its therapeutic benefit in an antibody-transfer model of erosive polyarthritis and to elucidate its potential to interfere with immune complex-dependent inflammatory pathways. Methods. Arthritis development was induced in male (BALB/c x B10.Q)F-1 mice by intravenous injection of two monoclonal antibodies specific for type II collagen and was quantified by clinical scoring and histopathology. Arthritis severity was assessed in a cohort of mice under systemic treatment with recombinant human ALP (daily doses of 0.1 mg for 5 days starting immediately after disease induction) in comparison with untreated controls. Concomitantly, functional assays (phagocytosis, oxidative burst, fluorescence-activated cell sorting analysis of integrin expression) were performed on neutrophils upon in vitro stimulation by IgG-coated latex beads. Results. ALP treatment reduced arthritis incidence and severity and had a protective effect against cartilage and bone erosion. ALP inhibited the conversion of the leukocyte beta2 integrins into an active conformation upon Fc receptor stimulation of granulocytes. ALP bound to the actin-bundling protein L-plastin and down-modulated filamentous actin assembly in response to stimulation with IgG-coated latex beads in granulocytes. ALP exerted additional inhibitory effects on neutrophil functions associated with cytoskeletal reorganization, such as phagocytosis and oxidative burst. Conclusion. In addition to its antiprotease activity, ALP exerts a variety of blocking effects on neutrophil functions, probably due to modulation of cytoskeletal changes, that may contribute to this inhibitor's antiarthritis potential and qualify it as a multifunctional regulator of inflammatory responses.}},
author = {{Sehnert, B and Cavcic, A and Bohm, B and Kalden, JR and Kutty Selva, Nandakumar and Holmdahl, Rikard and Burkhardt, H}},
issn = {{1529-0131}},
language = {{eng}},
number = {{7}},
pages = {{2347--2359}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Arthritis and Rheumatism}},
title = {{Antileukoproteinase - Modulation of neutrophil function and therapeutic effects on anti-type II collagen antibody-induced arthritis}},
url = {{http://dx.doi.org/10.1002/art.20339}},
doi = {{10.1002/art.20339}},
volume = {{50}},
year = {{2004}},
}