An essential role for mast cells as modulators of neutrophils influx in collagen-induced arthritis in the mouse

An essential role for mast cells as modulators of neutrophils influx in collagen-induced arthritis in the mouse

Author Pimentel, Tatiana Aparecida Autor UNIFESP Google Scholar
Franco Sampaio, Andre Luiz Google Scholar
D'Acquisto, Fulvio Google Scholar
Perretti, Mauro Google Scholar
Oliani, Sonia Maria Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Queen Mary Univ London
FarManguinhos FIOCRUZ
São Paulo State Univ UNESP
Abstract Mast cells are involved in immune disorders so that many of the proinflammatory and tissue destructive mediators produced by these cells have been implicated in the pathogenesis of rheumatoid arthritis. This scenario prompted us to investigate the correlation between mast cell degranulation and neutrophil influx within the digits and knees joints of arthritic mice assessing what could be the functional role(s) of joint mast cells in the response to collagen immunization. DBA/1J mice were submitted to collagen-induced arthritis and disease was assessed on day 21, 32 and 42 post-immunization. Pharmacological treatment with the glucocorticoid prednisolone, commonly used in the clinic, and nedocromil, a mast cell stabilizer, was performed from day 21 to 30. Arthritis develop after immunization, gradually increased up to day 42. Neutrophil infiltration peaked on day 32 and 21, in the digits and knees, respectively, showing an unequal pattern of recruitment between these tissues. This difference emerged for mast cells: they peaked in the digits on day 21, but a higher degree of degranulation could be measured in the knee joints. Uneven modulation of arthritis occurred after treatment of mice with prednisolone or nedocromil. Neutrophils migration to the tissue was reduced after both therapies, but only prednisolone augmented mast cell migration to the joints. Nedocromil exerted inhibitory properties both on mast cell proliferation and migration, more effectively on the digit joints. Thus, collagen induced an inflammatory process characterized by tissue mast cells activation and degranulation, suggesting a potential driving force in propagating inflammatory circuits yielding recruitment of neutrophils. However, the different degree of affected joint involvement suggests a time-related implication of digits and knees during collagen-induced arthritis development. These results provide evidence for local alterations whereby mast cells contribute to the initiation of inflammatory arthritis and may be targeted in intervention strategies. Laboratory Investigation (2011) 91, 33-42; doi:10.1038/labinvest.2010.140; published online 16 August 2010
Keywords collagen-induced arthritis
digits
knees
mast cells
nedocromil
neutrophils
prednisolone
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Wellcome Trust UK
Grant number FAPESP: 2005/51875-0
FAPESP: 2007/55348-0
CNPq: 306074/2007-9
Wellcome Trust UK: 083551/Z/07/Z
Date 2011-01-01
Published in Laboratory Investigation. New York: Nature Publishing Group, v. 91, n. 1, p. 33-42, 2011.
ISSN 0023-6837 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent 33-42
Origin http://dx.doi.org/10.1038/labinvest.2010.140
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000285694600004
URI http://repositorio.unifesp.br/handle/11600/33184

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