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Identification of Neutrophil Granule Protein Cathepsin G as a Novel Chemotactic Agonist for the G Protein-Coupled Formyl Peptide Receptor

Identification of Neutrophil Granule Protein Cathepsin G as a Novel Chemotactic Agonist for the G Protein-Coupled Formyl Peptide Receptor

Ronghua Sun, Pablo Iribarren, Ning Zhang, Ye Zhou, Wanghua Gong, Edward H Cho, Stephen Lockett, Oleg Chertov, Filip Bednar, Thomas J Rogers, Joost J Oppenheim, Ji Ming Wang

J Immunol. 2004 Jul 1;173(1):428-36.

PMID: 15210802

Abstract:

The antimicrobial and proinflammatory neutrophil granule protein cathepsin G (CaG) has been reported as a chemoattractant for human phagocytic leukocytes by using a putative G protein coupled receptor. In an effort to identify potential CaG receptor(s), we found that CaG-induced phagocyte migration was specifically attenuated by the bacterial chemotactic peptide fMLP, suggesting these two chemoattractants might share a receptor. In fact, CaG chemoattracts rat basophilic leukemia cells (RBL cells) expressing the high affinity human fMLP receptor FPR, but not parental RBL cells or cells transfected with other chemoattractant receptors. In addition, a specific FPR Ab and a defined FPR antagonist, cyclosporin H, abolished the chemotactic response of phagocytes and FPR-transfected cells to CaG. Furthermore, CaG down-regulated the cell surface expression of FPR in association with receptor internalization. Unlike fMLP, CaG did not induce potent Ca(2+) flux and was a relatively weaker activator of MAPKs through FPR. Yet CaG activated an atypical protein kinase C isozyme, protein kinase Czeta, which was essential for FPR to mediate the chemotactic activity of CaG. Thus, our studies identify CaG as a novel, host-derived chemotactic agonist for FPR and expand the functional scope of this receptor in inflammatory and immune responses.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42411912	Protein Kinase Cζ isozyme human			Price

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