Molecular Structures and Interactions of Pulmonary Surfactant Components

Authors


  • Note. This Review will be reprinted in EJB Reviews 1997 which will be available in April 1998.

J. Johansson, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden
Fax: +46 8 337462.

Abstract

The dominating functional property of pulmonary surfactant is to reduce the surface tension at the alveolar air/liquid interface, and thereby prevent the lungs from collapsing at the end of expiration. In addition, the system exhibits host-defense properties. Insufficient amounts of pulmonary surfactant in premature infants causes respiratory distress syndrome, a serious threat which nowadays can be effectively treated by airway instillation of surfactant preparations. Surfactant is a mixture of many molecular species, mainly phospholipids and specific proteins, surfactant protein A (SP-A), SP-B, SP-C and SP-D. SP-A and SP-D are water-soluble and belong to the collectins, a family of large multimeric proteins which structurally exhibit collagenous/lectin hybrid properties and functionally are Ca2+-dependent carbohydrate binding proteins involved in innate host-defence functions. SP-A and SP-D also bind lipids and SP-A is involved in organization of alveolar surfactant phospholipids. SP-B belongs to another family of proteins, which includes also lipid-interacting polypeptides with antibacterial and lytic properties. SP-B is a 17.4-kDa homodimer and each subunit contains three intrachain disulphides and has been proposed to contain four amphipathic helices oriented pairwise in an antiparallel fashion. SP-A, SP-B and SP-D all have been detected also in the gastrointestinal tract. SP-C, in contrast, appears to be a unique protein with extreme structural and stability properties and to exist exclusively in the lungs. SP-C is a lipopeptide containing covalently linked palmitoyl chains and is folded into a 3.7-nm α-helix with a central 2.3-nm all-aliphatic part, making it perfectly suited to interact in a transmembranous way with a fluid bilayer composed of dipalmitoylglycerophosphocholine, the main component of surfactant. Homozygous genetic deficiency of proSP-B causes lethal respiratory distress soon after birth and is associated with aberrant processing of the precursor of SP-C. This review focuses on the chemical composition, structures and interactions of the pulmonary surfactant, in particular the associated proteins.

Abbreviations.
CRD

carbohydrate recognition domain

FTIR

Fourier transform infrared

MBP

mannose binding protein

MD

molecular dynamics

PamOH

palmitic acid

Pam2GroPCho

1,2-dipalmitoyl-sn-glycero-3-phosphocholine

Pam2GroPGro

1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol

PtdCho

phosphatidylcholine

PtdGro

phosphatedylglycerol

PtdIns

phosphatidylinositol

PamCys

palmitovlcysteine

SP

surfactant protein

Ancillary