期刊
INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY
卷 22, 期 2, 页码 473-483出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/039463200902200224
关键词
Amyloid peptide; CD47 receptor; histamine secretion; integrin; mast cells; microglia; phagocytosis
资金
- Ligue Nationale Contre le Cancer
Mast cells are found in the brain, where they contribute to immune responses. They have been implicated in multiple sclerosis, but their potential role in Alzheimer's disease (AD), another inflammatory disease of the central nervous system, remains elusive. In the present study, we examined mast cell responses to amyloid beta (A beta) peptides 1-40 and 1-42, the major components of the Alzheimer amyloid plaques. Rat peritoneal mast cells were used as experimental model for human brain serosal mast cells. Fibrillar A beta 1-40 and A beta 1-42 peptides induced concentration-dependent exocytosis, as assessed by measurement of histamine secretion; exocytosis was reduced by pre-treatment with pertussis toxin and with antibodies against the CD47 receptor and the beta(1)-integrin subunit. Fibrillar A beta 1-40 and A beta 1-42 peptides coated on heat-inactivated yeast particles and soluble fibrillar A beta 1-40 and A beta 1-42 peptides were also recognized and phagocyted by mast cells. Uptake of the peptides was decreased in the presence of 4N1, a peptide agonist of the CD47 receptor, but remained unchanged in the presence of 4NGG, a peptide derived from 4N1 which does not bind to CD47. Non-fibrillar forms of A beta 1-40 and 1-42 peptides were unable to elicit mast cell responses. These results show that fibrillar A beta peptides can trigger mast cells and elicit exocytosis and phagocytosis. The A beta-induced activation of mast cells operates through a CD47/beta(1)-integrin membrane complex coupled with G(i)-protein. The present data support the hypothesis that mast cells, similarly to microglial cells, could play a major role in AD pathogenesis.
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