Roles of Group IIA Phospholipase A₂ and Complement in Killing of Bacteria by Acute Phase Serum

Abstract

The complement system is regarded as an important component of the innate defence system against invading bacteria. However, synergistic actions between the complement and the other components of innate immunity are incompletely known. Human group IIA phospholipase A 2 (hGIIA PLA 2 ) is an effective antibacterial enzyme in serum of patients with severe bacterial infections. Our aim was to investigate the significance of complement and hGIIA PLA 2 in acute phase serum. Serum samples were collected from patients with acute bacterial infections and from healthy control subjects. We prepared hGIIA PLA 2 -depleted serum by immunoadsorption and inhibited the activity of complement by a specific inhibitor, compstatin. The bactericidal effects of treated and untreated serum were compared by incubating Staphylococcus aureus and Listeria monocytogenes in the presence of serum. Acute phase serum effectively killed S. aureus and L. monocytogenes, and depletion of hGIIA PLA 2 significantly reduced the antibacterial effect. Complement had a weak bactericidal effect against L. monocytogenes. We conclude that hGIIA PLA 2 is the major antibacterial factor in human acute phase serum against the gram-positive bacteria S. aureus and L. monocytogenes, exceeding complement in efficiency.

At sPLA 2 -α nuclear relocalization by the Arabidopsis transcription factor AtMYB30 leads to repression of the plant defense response

“…Participation of sPLA 2 s in host defense, either as major antibacterial factors or as biologically active molecules modulating immune or inflammatory responses, has been documented in animal cells (25,26). Experimental evidence of the involvement of sPLA 2 s in plant defense is, in contrast, more limited.…”

Biology of Secretory Phospholipase A2

“…GIIA sPLA 2 is predominantly recognized as part of the innate immune system and appears to be a major antibacterial factor against Gram-positive bacteria in human acute phase serum [60][61][62]. A study of patients with sepsis showed that of the nine human sPLA 2 's, only GIIA sPLA 2 could be detected in serum by time-resolved fluoroimmunoassay [63].…”

“…[23], lung [25], liver, spleen, kidney, and ovary [30], brain [31] Digestion of dietary PLs [23], antibacterial [65], eicosanoid formation, cell contraction, proliferation [30], migration [11] PG > PS >> PC [44] M-type [40] II A Acute phase serum, intestinal mucosa, lacrimal gland cells, prostatic epithelial cells [36] Acute phase protein [1,35], antibacterial [60][61][62][64][65][66], cell proliferation [3,4], migration [5], apoptosis [6], atherogenic [124] PG > PS >> PC [44] M-, N-type [40] HSPG [41] C Pseudogene (human) [18] Testis, pancreas (mouse) [44] N/D PG >> PC [44] Low affinity to M-type [ High molecular weight [20]. Antiviral [78] PG > PC [44] Low affinity to M-type [40] V Heart, eye, pancreas [44], macrophages [99], neutrophils [69], mastocytes [70] Antibacterial [17,65], antiviral [77], atherogenic [137,142], AA release, eicosanoid generation …”

Purification and biochemical characterization of a secreted group IIA chicken intestinal phospholipase A2

“…a) 1 Unit: μmole of fatty acid released per min using egg yolk as substrate in the presence of 10 mM NaTDC and in the presence of 10 mM CaCl 2 .b) Proteins were estimated by Bradford method [30]. The experiments were conducted in triplicate.…”