Immunoregulatory functions of surfactant proteins

Key Points

  • Surfactant protein A (SP-A)and SP-D are members of a family of immune proteins known as collectins, or collagen-like lectins.

  • SP-A and SP-D interact with various pathogens through their lectin domains and enhance pathogen uptake by phagocytes.

  • SP-A and SP-D regulate functions of a variety of immune cells, including dendritic cells, T cells, neutrophils and macrophages.

  • SP-A- and SP-D-null mice have an increased susceptibility to infection and inflammation.

  • Recent studies indicate that SP-A and SP-D might function at sites in addition to the lung, where they were first discovered and are most abundant.

  • SP-A has been shown to initiate an inflammatory response in the uterus and to induce labour.

Abstract

Because the lungs function as the body's gas-exchange organ, they are inevitably exposed to air that is contaminated with pathogens, allergens and pollutants. Host-defence mechanisms within the lungs must facilitate clearance of inhaled pathogens and particles while minimizing an inflammatory response that could damage the thin, delicate gas-exchanging epithelium. Pulmonary surfactant is a complex of lipids and proteins that enhances pathogen clearance and regulates adaptive and innate immune-cell functions. In this article, I review the structure and functions of the surfactant proteins SP-A and SP-D in regulating host immune defence and in modulating inflammatory responses.

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Figure 1: Lung host-defence mechanisms.
Figure 2: Collectin and C1q structure.
Figure 3: Functions of SP-A and SP-D.
Figure 4: Collectin receptors.
Figure 5: Surfactant proteins regulate dendritic-cell and T-cell functions, thereby providing a link between innate and adaptive immunity.
Figure 6: Surfactant protein A signals the initiation of parturition.

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Acknowledgements

My sincere thanks to S. L. Young and to Wright Lab members, M. Bolger, K. Evans, S. Giles, R. Lovingood, D. Malherbe, J. Malloy and M. Reidy, for their critical review of the manuscript. I extend my sincere apologies to those colleagues whose original work could not be cited due to space limitations. My laboratory is supported by grants from the National Institutes of Health (United States).

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DATABASES

Entrez Gene

ABCA3

C1qR

calreticulin

CCL2

CD91

CL-43

CL-46

CL-L1

CL-P1

conglutinin

CXCL12

gp340

IFN-γ

MBL

NF-κB

scavenger receptor A

SIRP-α

SP-A

SP-B

SP-C

SP-D

TGF-β

TLR2

TLR4

TNF

Glossary

RESPIRATORY-DISTRESS SYNDROME

A disease that affects premature newborns, resulting in increased difficulty in breathing. The disease is caused by a lack of surfactant, which helps to keep the lungs from collapsing.

CHRONIC OBSTRUCTIVE PULMONARY DISEASE

(COPD). A group of lung diseases in which air-flow is limited and there is airway inflammation and destruction of lung tissue.

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Wright, J. Immunoregulatory functions of surfactant proteins. Nat Rev Immunol 5, 58–68 (2005). https://doi.org/10.1038/nri1528

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