In resolving acute inflammation, specialized pro-resolving mediators (SPMs) are generated. Lipoxin A4 (LXA4) is derived from arachidonic acid via the 15-lipoxygenase pathway. Which of the following correctly describes the mechanism by which LXA4 actively terminates neutrophil-dominant inflammation?
- A LXA4 competitively inhibits COX-2, preventing conversion of arachidonic acid to prostaglandins
- B LXA4 activates mast cells to secrete IL-10, indirectly inhibiting neutrophil production by suppressing G-CSF from bone marrow stroma
- C LXA4 activates PPAR-γ in macrophages, causing M2 polarization and secretion of IL-13 that inhibits neutrophil degranulation
- D LXA4 binds FPR2/ALX receptors on neutrophils and epithelial cells, inhibiting NF-κB-driven cytokine expression, reducing L-selectin shedding, downregulating LTB4-stimulated neutrophil chemotaxis, and promoting macrophage efferocytosis of apoptotic neutrophils ✓
Explanation
Lipoxin A4 (LXA4) is a key endogenous stop signal of acute inflammation. It signals via the GPCR FPR2/ALX (formyl peptide receptor 2/lipoxin A4 receptor) on neutrophils, inhibiting LTB4-induced chemotaxis and transendothelial migration, stimulating apoptosis of recruited neutrophils, and promoting their phagocytic clearance (efferocytosis) by macrophages. On macrophages, LXA4 upregulates efferocytosis capacity and suppresses pro-inflammatory cytokine production. This 'active resolution' (not passive decay) is the physiological mechanism that terminates acute inflammation, preventing chronic inflammation; defects in LXA4 signaling underlie persistent inflammatory states like bronchial asthma.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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