α1-Acid glycoprotein production in rat dorsal air pouch in response to inflammatory stimuli, dexamethasone and honey bee venom

Abstract

This study shows the rapid and differential production of the 40–43 kDa and the 70–90 kDa α1-acid glycoprotein (AGP) fucosylated glycoforms after treatment of the dorsal air pouch with bacterial lipopolysaccharide (LPS), HgCl 2 or Freund's complete adjuvant (FCA). The 40–43 kDa and the 70–90 kDa AGP production is peaked 1–3 h post-LPS treatment. We observed that the responses to LPS and FCA are similar in that both AGP isoforms are induced whereas they differ in that the FCA exhibits a 6 h lag period. The response to HgCl 2, however, exhibits the specific biphasic induction only of the 40–43 kDa AGP. The serum 40–43 kDa AGP glycoform gradually increases in response to all of the above stimulants and peaks by 24 h post- treatment. The increase of the 70–90 kDa AGP levels in the air pouch occurs in association with the accumulation of polymorphonuclear (PMN) cells while dexamethasone (DEX) increases only the 40–43 kDa AGP production in the absence of PMN accumulation. Macrophage–monocyte lineage cells forming the air pouch lining tissue may potentially be the cells that secrete the 40–43 kDa AGP while polymorphonuclear cells that infiltrate the air pouch secrete the 70–90 kDa AGP. The 40–43 kDa and 70–90 kDa AGP production induced by LPS in the air pouch precedes that of interleukin-1 (IL-1) or interleukin-6 (IL-6) while the 40–43 kDa AGP glycoform potentially increases IL-6 production by air pouch PMN exudate cells. These significant differences suggest a local pro-inflammatory role of AGP. Honeybee venom suppressed arthritis development and exhibited differential local or systemic regulation of AGP in serum vs. air pouch exudate or synovial fluid. This study with the air pouch model of facsimile synovium tissue suggests that local α1-acid glycoprotein (AGP) production may contribute to pro-inflammatory and anti-inflammatory activities during the local acute phase response or during chronic inflammatory stress as in arthritis.