Chemotactic activity and receptor binding of neutrophil attractant/activation protein-1 (NAP-1) and structurally related host defense cytokines: Interaction of NAP-2 with the NAP-1 receptor

E. J. Leonard, T. Yoshimura, A. Rot, K. Noer, A. Walz, M. Baggiolini, D. A. Walz, E. J. Goetzl, C. W. Castor

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

Neutrophil attractant/activation protein-1 (NAP-1) has sequence similarity to platelet factor-4 (PF-4) and to NAP-2 (a truncated form of connective tissue activating protein-III [CTAP-III(des 1-15)]. We compared chemotactic activity for neutrophils of these related proteins. We also included for comparison CTAP-III, CTAP-III(des 1-13), the C-terminal dodecapeptide of PF-4 [PF-4(59-70)], and C5a. Chemotactic potency (EC50) was highest for NAP-1 and C5a. Although chemotactic efficacy (peak percentage of neutrophils migrating) was comparable for C5a, NAP-1, and NAP-2, the NAP-2 response occurred only at concentrations 100-fold higher than the NAP-1 EC50 of 10-8 M. Data for the CTAP-III proteins confirmed that CTAP-III is not an attractant and that chemotactic activity appears as a result of cleavage of residues at the N-terminus to make CTAP-III(des 1-13) or NAP-2 [CTAP-III(des 1-15)]. Chemotactic activity of PF-4 was low and variable, with no significant response by neutrophils from six of nine subjects. In contrast, PF-4 (59-70) regularly induced high chemotactic responses, although the EC50 of 1.6 x 10-5 M was 1,000-fold greater than that of NAP-1. The binding of fluoresceinated NAP-1 to neutrophils was inhibited by unlabeled NAP-1 or NAP-2 but not by PF-4 or PF-4 (59-70). This suggests that NAP-2 interacts with the neutrophil NAP-1 receptor. Despite the low chemotactic potency of NAP-2, it is a potential attractant at sites of injury because of the relatively large amounts of the parent CTAP-III released from platelets, as indicated by a serum concentration of approximately 10-6 M.

Original languageEnglish
Pages (from-to)258-265
Number of pages8
JournalJournal of Leukocyte Biology
Volume49
Issue number3
DOIs
Publication statusPublished - 1991
Externally publishedYes

Keywords

  • CTAP-III
  • PF-4
  • connective tissue activating peptide-III
  • flow cytometry
  • interleukin-8
  • platelet
  • platelet factor-4

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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