Emergence of a metalloproteinase/phospholipase A₂ axis of systemic inflammation

Figures & data

Figure 1 The postulated mechanism of PLA₂ regulation by MMPs via cytokines gives rise to many plausible PLA₂-mediated signaling events that can impact target tissues at short and long distances. Alternate signaling pathways and feedback regulatory loops (dashed arrows) are likely part of the complex regulation of target tissues by MMPs.

Abbreviations: PLA_2, phospholipase A₂; sPLA₂, secreted PLA₂; cPLA₂, calcium-dependent PLA₂; iPLA₂, calcium-independent PLA₂; MMPs, matrix metalloproteinases; MCP-3, monocyte chemoattractant protein-3.

Table 1 Possible MMP/cytokine/PLA₂ axis subtypes

MMP	Cytokine substrate	Target cell	PLA2	Function	References
MMP-1/3	MCP-1	Blood monocytes	iPLA2β cPLA2α	Chemotaxis	80, 94
MMP-1/3	MCP-1	Endothelial cells, macrophages	PLA2G5, Lp-PLA2	Pro-atherogenic modification of LDL, monocyte recruitment into arterial wall (atherosclerosis)	95-97
MMP-2	MCP-3	Cardiac cells	Cardiac sPLA2	Blood pressure homeostasis, cardiac PGE2 production, cardiac lipid metabolism, fever	60
MMP-9/12	IL-8	Synovial fibroblast-like cells	cPLA2	Rheumatoid arthritis (inflammation, joint destruction)	98–102

Abbreviations: MMP, matrix metalloproteinase; MCP, monocyte chemoattractant protein; PLA_2, phospholipase A₂; sPLA₂, secreted PLA₂; cPLA₂, calcium-dependent PLA₂; iPLA₂, calcium-independent PLA₂; IL, interleukin; PGE₂, prostaglandin E₂; Lp-PLA₂m, Lipoprotein-associated PLA₂.