By Binding SIRPa or calreticulin/CD91, Lung Collectins Act as Dual Function Surveillance Molecules to Suppress for Enhance Inflammation

(Gardai, S. J. et al, 2003, Cell, 115: 13-23)

Speaker: 陳毓雯

Commentator: 王志堯 老師

Time: 14:00~15:00 12/24/2003

Place: Room 602

Abstract:

   Collectins are components of the innate immune system. They are characterized by lectin-globular heads and collagen tails. The globular heads are able to recognize pathogen-associated molecular patterns (PAMPs) that lead to exposure of the tail to carry out pathogen clearance functions (opsonization for example) (1). Surfactant protein A and surfactant protein D (SP-A and SP-D) are members of the collectin family in the lung. However, while some studies indicate that they inhibit inflammation (2), other reports found that they can enhance inflammation (3). In this article, the authors provide evidence to resolve the conflict by describing a model in which lung collectins have dual functions. In normal conditions (non-infectious conditions), SP-A and SP-D can bind to signal inhibitory regulatory protein a (SIRPa, the membrane containing ITIM domain) and act on SHP-1 phosphatase to initiate a signaling pathway to block proinflammatory molecule production. In contrast, in an infectious environment SP-A and SP-D can recognize PAMPs on foreign organisms or damaged cells. They then present their collagen tail to signal through careticulin/CD91 pathway to promote phagocytosis and proinflammatory response. The dual function model also can explain how the lung can maintain non-inflammatory environment while faced with daily particle inhaling and high oxygen tension.

Reference:

1.      Francis, X. M. et al., 2002. The pulmonary collectins, SP-A and SP-D, orchestrate innate immunity in the lung. J Clin Invest. 109: 707–712.

2.      Bridges, J. P. et al., 2000. Pulmonary surfactant proteins A and D are potent endogenous inhibitors of lipid peroxidation and oxidative cellular injury. J. Biol. Chem. 275: 33848-38855.

3.      Kremiev, S. G. et al., 1994. Surfactant protein A stimulation of inflammatory cytokine and immunoglobulin production. Am. J. Physiol. 267: L712-L719.