Type Ii Secretory Phospholipase A2

Type II secretory phospholipase (sPLA2-II) is another well-studied member ofthe phos-pholipase 2 family. The sPLA2 family consists of a type I enzyme secreted by the pancreas (so-called pancreatic PLA2) and a type II PLA2 with wide tissue expression (hepatocytes, macrophages, endothelial cells, platelets, and vascular SMCs [VSMCs]) (48,49). sPLA2-II is a Ca2+-dependent, 14-kDa enzyme that belongs to the group of acute-phase reactants. Circulating levels of sPLA2-II increase greatly during systemic inflammatory conditions, such as during sepsis, rheumatoid arthritis, or inflammatory bowel disease (50). Moreover, sPLA2-II production is upregulated in response to proinflammatory compounds such

Fig. 2. Proatherogenic mechanisms of sPLA2-IIA. ApoB-containing lipoproteins and sPLA2-IIA, through their interaction with arterial proteoglycans, may facilitate enzymatic hydrolysis of lipoprotein phospholipids. Nonesterified fatty acids (NEFAs), oxidized NEFAs, and lysophosphatidylcholine (Lyso-PC) bind albumin or remain associated with modified lipoproteins. This can induce aggregation and fusion of the lipoproteins, processes that are enhanced by intima proteoglycans. sPLA2-IIA-mod-ified LDL can be further modified by sphingomyelinase (SMase) and 15-lipoxygenase (15-LO). NEFAs, oxidized NEFAs, and Lyso-PC may induce proinflammatory cellular processes, such as expression of adhesion molecules by endothelial cells, monocyte migration, and differentiation into macrophages, thereby increasing secretion of proteoglycans by SMCs. Local release of cytokines can stimulate the synthesis and secretion of sPLA2-IIA. MMPs, matrix metalloproteinases; IEL, internal elastic lamina. (Reproduced from ref. 52 with permission from Lippincott Williams & Wilkins, Copyright 2004.)

Fig. 2. Proatherogenic mechanisms of sPLA2-IIA. ApoB-containing lipoproteins and sPLA2-IIA, through their interaction with arterial proteoglycans, may facilitate enzymatic hydrolysis of lipoprotein phospholipids. Nonesterified fatty acids (NEFAs), oxidized NEFAs, and lysophosphatidylcholine (Lyso-PC) bind albumin or remain associated with modified lipoproteins. This can induce aggregation and fusion of the lipoproteins, processes that are enhanced by intima proteoglycans. sPLA2-IIA-mod-ified LDL can be further modified by sphingomyelinase (SMase) and 15-lipoxygenase (15-LO). NEFAs, oxidized NEFAs, and Lyso-PC may induce proinflammatory cellular processes, such as expression of adhesion molecules by endothelial cells, monocyte migration, and differentiation into macrophages, thereby increasing secretion of proteoglycans by SMCs. Local release of cytokines can stimulate the synthesis and secretion of sPLA2-IIA. MMPs, matrix metalloproteinases; IEL, internal elastic lamina. (Reproduced from ref. 52 with permission from Lippincott Williams & Wilkins, Copyright 2004.)

as interleukin (IL)-1^, IL-6, tumor necrosis factor (TNF)-a, interferon (IFN)-y, and oxLDL (50-53).

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Arthritis Joint Pain

Arthritis Joint Pain

Arthritis is a general term which is commonly associated with a number of painful conditions affecting the joints and bones. The term arthritis literally translates to joint inflammation.

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