There are four main surfactant proteins, known as SP-A, B, C, and D. SP-A and D are hydrophilic, while SP-B and C are hydrophobic. Proteins are very sensitive to experimental conditions (temperature, pH, concentration, substances such as calcium, and so on). Moreover, their effects tend to overlap. Thus, it is difficult to pinpoint the specific role of each protein.

SP-A and SP-D

These two proteins are hydrophilic. They are built of trimers:

(Haagsman and Diemel, 2001, online)

Both proteins have a role in the immune system and can be found in other areas of the body.

SP-A

SP-A was the first surfactant protein to be identified, and is also the most abundant. (Ingenito et al., 1999, Theory binder) Its molecular mass varies from 26-38 kDa. (Pérez-Gil et al., 1998, binder)

The protein has a "bouquet" structure of six trimers:

(Haagsman and Diemel, 2001, online)

It can be found in an open or closed form depending on the other substances present in the system. Calcium ions produce the closed-bouquet form. (Palaniyar et al., 1998, SP-A and D online)

Roles of SP-A

• Immune system
• Protect surfactant from negative effects of serum proteins
• Surfactant transport/ adsorption (with other proteins)

  SP-A is necessary for the production of tubular myelin, a lipid transport structure unique to the lungs. Tubular myelin consists of square tubes of lipid lined with protein:

  

  (Palaniyar et al., 2001, SP-A and D online)

Mice genetically engineered to lack SP-A have normal lung structure and surfactant function. It is possible that SP-A's beneficial surfactant properties are only evident under situations of stress. (Korfhagen et al., 1996, SP-A and D online)

SP-D

At 43 kDa, SP-D is the largest surfactant protein. (Pérez-Gil and Keough, 1998, binder) It is usually found with Type II cells, which excrete surfactant components, rather than at the air-water interface.

SP-D is a dodecamer:

(Haagsman and Diemel, 2001, online)

Roles of SP-D

• Immune system
• Regulate surfactant balance

  Genetically altered mice without SP-D have three to four times more phospholipid than normal. The proportion of SP-A and C is correspondingly reduced. In SP-D null mice, the macrophages (large cells involved in the immune system) have a foamy appearance, and are larger and possibly more numerous. After several months, these mice develop emphysema, a condition in which pulmonary air sacs are unnaturally large. (Botas et al., 1998, SP-A and D binder)

SP-B and SP-C

SP-B and SP-C are hydrophobic proteins. They are directly involved in protein respreading. However, they bind preferentially to anionic lipids, not DPPC. (Pérez-Gil and Keough, 1998, binder)

SP-B

SP-B is 8.7 kDa. (Pérez-Gil and Keough, 1998, binder) It consists of alpha-helices with disordered links. One model for its structure suggests that two sets of positive helices border two neutral domains:

(Krol et al., 2000, SP-B and C binder)

Roles of SP-B

• Tubular myelin component
• Enhance adsorption and respreading

  SP-B is necessary for lung function. Humans with genetic SP-B dysfunction die soon after birth, as do genetically engineered SP-B null mice. Lack of SP-B is linked to improper processing of SP-C, so its effect cannot be entirely isolated. (Hawgood et al., SP-B and C binder)

  SP-B can fluidize a monolayer by preventing lipid packing. This leads to smaller domains in a liquid-condensed state, and makes widespread collapse more difficult. (Krol et al., 2000, SP-B and C binder)

  SP-B may also promote buckling and other reversible collapse structures. Here is one model:

  

  (Krol et al., 2000, SP-B and C binder)

SP-C

SP-C is the smallest surfactant protein, at 4.2 kDa. (Pérez-Gil and Keough, 1998, binder) It is also one of the more abundant; estimates for the ratio of SP-B to SP-C range from 1:2 to 1:10. (c.f. Krol et al., 2000, SP-B and C binder and Veldhuizen et al., 2001, SP-B and C online) SP-C's main structural feature is an alpha-helix, exactly the right length to span a lipid bilayer.

(Pérez-Gil and Keough, 1998, binder)

SP-C is the most hydrophobic of all the surfactant proteins, and is only found in the lungs.

Roles of SP-C

• Enhance the rate of adsorption
• In vitro, SP-C promotes multi-layered, stacked structures. It has been suggested that SP-C can act as a lever to move lipids.

  

  (Galla et al., 1998, SP-B and C online)

• In vivo, lack of SP-C may cause problems at low lung volumes.

  SP-C null mice demonstrate some abnormalities in breathing at these volumes, and bubbles of their surfactant are unstable when compressed in the captive bubble surfactometer. Thus, SP-C may have a stabilizing effect on highly compressed surfactant. (Glasser et al., SP-B and C binder)