Was the appearance of surfactants in air breathing vertebrates ultimately the cause of decompression sickness and autoimmune disease?

• Surfactants were essential when vertebrates ventured into air breathing.
• Surfactants leak into the blood forming hydrophobic spots, and nanobubbles develop.
• Nanobubbles become gas micronuclei and decompression bubbles.
• Proteins deformed at a gas phase may be recognized as foreign by the immune system.
• Surfactant spots may be the cause of decompression sickness and autoimmune disease.

All air breathing vertebrates are endowed with pulmonary surfactants, surface-active lipoprotein complexes formed by type II alveolar cells. Surfactants are deposited in clearly defined areas on the luminal aspect of blood vessels, producing hydrophobic spots. Gas nanobubbles measuring 5–100 nm form spontaneously on the smooth hydrophobic spot from dissolved gas. Bubbles nucleate and grow at these spots after decompression from high pressure. Proteins with hydrophobic regions circulating in the blood will adhere to the gas phase-plasma interface. Deformation of their secondary and tertiary configuration will present them as foreign molecules or autoantigens. Components of the intact protein which are also present in a deformed protein may be recognized as foreign too. This process is proposed as the trigger for autoimmune diseases. The presence of autoimmune disease in air breathing vertebrates, increased autoimmunity and the elevated risk of decompression sickness with age, as well as variable sensitivity to both diseases, can be matched with the appearance of surfactant spots. Eliminating these spots may provide protection against both diseases.