Mapping of the C5a receptor signal transduction network in human neutrophils.

AUTOR(ES)

Buhl, A M

RESUMO

Human neutrophils respond to chemoattractants, resulting in their accumulation at an inflammatory site. Chemoattractants such as the C5a peptide, derived from the C5 complement factor, bind to inhibitory guanine nucleotide binding protein (Gi)-coupled seven membrane-spanning receptors expressed in neutrophils. C5a receptor activation results in the Gi-dependent activation of the mitogen-activated protein (MAP) kinase pathway in human neutrophils. C5a receptor ligation activates both B-Raf and Raf-1, with B-Raf activation overlapping but temporally distinct from that of Raf-1. B-Raf and Raf-1 both efficiently phosphorylate MAP kinase kinase (MEK-1). C5a also stimulates guanine nucleotide exchange and activation of Ras. Ras and Raf activation in response to C5a involves protein kinase C-dependent and -independent pathways. Activation of both Raf-1 and B-Raf was inhibited by protein kinase A stimulation, consistent with the inhibitory effects of increased cAMP levels on neutrophil function. The findings define a functional signal transduction pathway linking the neutrophil C5a chemoattractant receptor to the regulation of Ras, B-Raf, Raf-1, and MAP kinase.

Documentos Relacionados

• Increased C5a receptor expression in sepsis
• Demonstration of specific C5a receptor on intact human polymorphonuclear leukocytes.
• Purification of the active C5a receptor from human polymorphonuclear leukocytes as a receptor-Gi complex.
• Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome
• Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome