Serum amyloid A: action on leukocytes and possible participation in the maintenance of the chronic inflammatory state in diabetes

Author(s)

Elaine Hatanaka

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2005-02-01

Examining board members

Ana Campa; Rui Curi; Zuleica Bruno Fortes; Primavera Borelli Garcia; Maria Teresa Zanella

• Advisor: Ana Campa
• Field of knowledge: Biological Sciences - Biochemistry
• Indexed in: Banco de Dados Bibliográficos da USP-DEDALUS
• Location: Universidade de São Paulo. Biblioteca do Conjunto das Químicas; CQ T/616.07; H361a

Abstract

We previously described that the acute phase protein serum amyloid A (SAA) is a potent stimulus for the expression and release of TNF-α, IL-8 and IL-1β(1, 2, 3, 4). The signaling involved in this process was here studied through the effect of signaling inhibitors. The participation of MAPK, PI-3K pathways, Gi protein coupled receptors and the NF-kB on the signaling cascade was indirect evidenced (2, 3). The NADPH oxidase system seems to be not required in the release of cytokines promoted by SAA because neutrophils from patients with Chronic Granulomatous Disease (CGD - NADPH system deficiency) also responded to SAA. Indeed neutrophils from CGD patients release larger amounts of IL-8 and TNF-α than neutrophils from control individuals, under basal and stimulated conditions (5). Moreover SAA showed to be a priming agent rendering the neutrophils more responsive to opsonized particles (6). These data reinforce our hypothesis that SAA has a participation in the progression of chronic diseases in wich the serum concentration of this protein is permanently increased. To evaluate the proinflammatory character of SAA we choosen diabetes mellitus type 2. This study makes the novel observation that neutrophils and mononuclear cells of diabetics were more responsive to SAA in the induction of the proinflammatory cytokine IL-1β and the proangiogenic and chemotactic protein IL-8 secretion. Cell migration wa also increased. It is well known that patients with diabetes mellitus have an increased prevalence of vascular disease and correlation exists between the increased prevalence of vascular disease and cytokine production. Thus, we believe that the hyperresponsivity of leukocytes to SAA may be relevant to the proinflammatory conditions associated to vascular complications in diabetic patients. (AU)