Lung Collectins Both Enhance and Suppress Immune Response

Researchers have shown that the two lung collectins, surfactant proteins A and D (SP-A and SP-D), act in a dual manner to enhance or suppress inflammatory mediator production depending on binding orientation.

Collectin (collagen-like lectin) is a subgroup of C-type (i.e., calcium-dependent) animal lectins characterized by the presence of collagen-like sequences (Gly-Xaa-Yaa triplet). The collectins include three serum proteins, mannan-binding protein (MBP), bovine conglutinin and bovine collectin-43 (CL-43), and two lung surfactant proteins (SP-A and SP-D). The collectins bind to terminal nonreducing sugar residues, mannose, GlcNAc, fucose, and glucose. SP-D binds to maltose. They play important roles in innate immunity without involvement of antibodies.

Surfactant proteins A and D are composed of two regions; a globular head domain that binds pathogen-associated molecular patterns (PAMPs, conserved cell-surface structures that are unique to bacteria and are recognized by the innate sector of the immune system) and a collagenous tail domain that initiates phagocytosis.

Investigators at National Jewish Medical and Research Center (Denver, CO, USA; www.njc.org) working with mice found that SP-A and SP-D bind PAMPs through their globular heads to initiate a signaling pathway that blocks proinflammatory mediator production. In contrast, their collagenous tails stimulate proinflammatory mediator production through binding to calreticulin/CD91. These findings were published in the October 3, 2003, issue of Cell.

"The lung collectins can effectively discriminate between conditions in the lung that warrant an immune response and those that do not,” explained senior author Dr. Peter Henson, professor of pediatrics at National Jewish Medical and Research Center. "They do this with a clever mechanism, inhibiting the immune response with one end of their structure and promoting it with the other. These findings should help clarify confusion about the lung collectins. Lung collectins play not one role, but two as they protect the lung not only from harmful pathogens, but also from harmful overreaction by the immune system.”



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