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2016 ; 274
(1
): 9-15
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Evolution of the complement system: from defense of the single cell to guardian
of the intravascular space
#MMPMID27782327
Elvington M
; Liszewski MK
; Atkinson JP
Immunol Rev
2016[Nov]; 274
(1
): 9-15
PMID27782327
show ga
The complement system is an evolutionarily ancient component of immunity that
revolves around the central component C3. With the recent description of
intracellular C3 stores in many types of human cells, our view of the complement
system has expanded. In this article, we hypothesize that a primitive version of
C3 comprised the first element of the original complement system and initially
functioned intracellularly and on the membrane of single-celled organisms. With
increasing specialization and multicellularity, C3 evolved a secretory capacity
that allowed it to play a protective role in the interstitial space. Upon
development of a pumped circulatory system, C3 was synthesized in large amounts
and secreted by the liver to protect the intravascular space. Recent discoveries
of intracellular C3 activation, a C3-based recycling pathway and C3 being a
driver and programmer of cell metabolism suggest that the complement system
utilizes C3 to guard not only extracellular but also the intracellular
environment. We predict that the major functions of C3 in all four locations
(i.e. intracellular, membrane, interstitium and circulation) are similar:
opsonization, membrane perturbation, triggering inflammation, and metabolic
reprogramming.