Cigarette smoke can activate the alternative pathway of complement in vitro by modifying the third component of...

Area of Science:

• Immunology
• Biochemistry

Background:

• Cigarette smoking increases pulmonary immune cells like phagocytes and neutrophils.
• Complement component 5a (C5a) is a chemoattractant for these cells, generated during complement (C) activation.

Purpose of the Study:

• To investigate if cigarette smoke can activate the complement system in vitro.
• To identify the components in cigarette smoke responsible for complement activation.

Main Methods:

• Hemolytic capacity assays of human serum treated with cigarette smoke extract.
• Analysis of complement component 3 (C3) modification using electrophoresis and susceptibility to regulatory proteins.
• Complement pathway activation assays using serum with specific inhibitors.

Main Results:

• Aqueous whole cigarette smoke, but not filtered gas, depleted serum hemolytic capacity.
• Smoke factors (mol wt < 1,000) activated the alternative complement pathway via C3 modification.
• Smoke-modified C3 showed altered electrophoretic mobility and reduced interaction with complement regulatory proteins H and I.

Conclusions:

• Cigarette smoke contains factors that activate the alternative complement pathway through C3 modification.
• This in vitro complement activation by smoke may contribute to pulmonary inflammation observed in smokers.