A role for human Sp alpha as a pattern recognition receptor.

Area of Science:

• Immunology
• Molecular Biology
• Biochemistry

Background:

• Human Sp alpha is a soluble protein in the scavenger receptor cysteine-rich (SRCR) superfamily, primarily expressed by macrophages in lymphoid tissues.
• Its role in regulating innate and adaptive immune systems is largely unknown, though it binds to immune cells.

Purpose of the Study:

• To investigate the functional role of human Sp alpha in the innate immune response.
• To determine if human Sp alpha interacts with bacterial components and modulates immune cell activity.

Main Methods:

• Recombinant human Sp alpha (rSp alpha) was used to study binding to bacterial strains (Gram-positive and Gram-negative).
• Competition studies identified binding sites for lipoteichoic acid (LTA) and lipopolysaccharide (LPS).
• The bacterial binding activity of the SRCR domain 1 was assessed, and rSp alpha's effect on tumor necrosis factor-alpha secretion by monocytes was measured.

Main Results:

• Recombinant human Sp alpha (rSp alpha) binds to both Gram-positive and Gram-negative bacteria via recognition of LTA and LPS, respectively.
• The conserved regions of LPS (2-keto-3-deoxyoctulosonic acid and lipid A) are involved in Sp alpha recognition.
• A single SRCR domain (domain 1) of Sp alpha contains both LPS and LTA binding sites.
• rSp alpha induced bacterial aggregation and inhibited LPS/LTA-stimulated tumor necrosis factor-alpha secretion by human monocytes.

Conclusions:

• Human Sp alpha binds to conserved bacterial surface components, indicating a direct role in host defense against bacterial infections.
• Sp alpha acts as an active component of the innate immune response by binding bacteria and modulating monocyte inflammatory responses.