The acute‐phase protein α1‐acid glycoprotein (AGP) induces rises in cytosolic Ca2+ in neutrophil granulocytes via sialic acid binding immunoglobulin‐like lectins (Siglecs)

We studied whether the acute‐phase protein α1‐acid glycoprotein (AGP) induces rises in [Ca2+]i in neutrophils and sought to identify the corresponding AGP receptor (or receptors). We found that AGP elicited a minimal rise in [Ca2+]i in Fura‐2‐loaded neutrophils, and this response was markedly enhanced by pretreatment with anti‐L‐selectin antibodies. (The EC50 value of the AGP‐induced Ca2+ response was 9 μg/ml.) Activation of phospholipase‐C, Src tyrosine kinases, and PI3 kinases proved to be essential for the AGP‐mediated increase in [Ca2+]i, whereas the p38 MAPK and SYK signaling pathways were not involved. Furthermore, antibodies against sialic acid binding, immunoglobulin‐like lectin 5 (Siglec‐5) and oligosac‐charide 3′‐sialyl‐lactose both antagonized the AGP‐in‐duced response and caused an immediate increase in [Ca2+]i in anti‐L‐selectin‐treated neutrophils, which indicates a signaling capacity of Siglec‐5. We used modified forms of AGP (treated with mild periodate or neuraminidase) to establish the importance of sialic acid residues. The modified forms of AGP caused a much smaller rise in [Ca2+]i than did unaltered AGP. Affinity chromatography confirmed that unchanged AGP, but not neuraminidase‐treated AGP, bound to Siglec‐5. Our report provides the first evidence for a signaling capacity by AGP through a defined receptor. Pre‐engagement of L‐selectin significantly enhanced this signaling capacity.— Gunnarsson, P., Levander, L., Påhlsson, P., Grenegård, M. The acute‐phase protein α1‐acid glycoprotein (AGP) induces rises in cytosolic Ca2+ in neutrophil granulocytes via sialic acid binding immunoglobulin‐like lectins (Siglecs). FASEB J. 21, 4059–4069 (2007)

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