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Blood, 1 May 2001, Vol. 97, No. 9, pp. 2854-2862
PHAGOCYTES
Identification of novel chemoattractant peptides for
human leukocytes
Yoe-Sik Bae,
Hyunjoo Bae,
Youndong Kim,
Taehoon G. Lee,
Pann-Ghill Suh, and
Sung Ho Ryu
From the Division of Molecular and Life Sciences,
Pohang University of Science and Technology, Korea.
Superoxide is the most important armory on the primary defense line
of monocytes against invading pathogens, and the identification of new
stimuli and the characterization of the regulatory mechanism of
superoxide generation are of paramount importance. In this study, we
identified 3 novel peptides by screening a synthetic hexapeptide
combinatorial library and modification of 1 of the peptides. The
isolated peptides that can induce superoxide generation in human
monocytes are His-Phe-Tyr-Leu-Pro-Met-CONH2 (HFYLPM), Met-Phe-Tyr-Leu-Pro-Met-CONH2 (MFYLPM), and
His-Phe-Tyr-Leu-Pro-D-Met-CONH2 (HFYLPm). All 3 peptides
also caused intracellular calcium ([Ca++]i)
rise. We tested the specificities of the peptides on cells of different
origin by looking at [Ca++]i rise. All 3 peptides acted specifically on leukocytes and not on nonimmune cells.
Among leukocytes, HL60 and Jurkat T cells were stimulated specifically
by MFYLPM or HFYLPM, respectively. As a physiologic characteristic of
the peptides, we observed that all 3 peptides induced chemotactic
migration of monocytes. Studying receptor specificity, we concluded
that the 3 peptides might act on some shared and some distinct
receptor(s) on leukocytes. Studying intracellular signaling set in
motion by the peptides revealed that HFYLPM, but not MFYLPM or HFYLPm,
induced chemotaxis via phospatidylinositol-3 kinase and protein kinase
C. Because HFYLPM, MFYLPM, and HFYLPm not only exhibit different
specificities depending on cell type and status of differentiation but
also stimulate cells via distinct receptors and signaling, the 3 novel
peptides might be useful tools to study leukocyte activation.

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