Hemokinin is a hematopoietic-specific tachykinin that regulates B lymphopoiesis

Nat Immunol. 2000 Nov;1(5):392-7. doi: 10.1038/80826.

Abstract

We report here the molecular cloning of a newly identified preprotachykinin gene, Pptc, which specifies the sequence for a new preprotachykinin protein and bioactive peptide designated hemokinin 1 (HK-1). PPT-C mRNA was detected primarily in hematopoietic cells in contrast to the previously described Ppta and Pptb genes, which are predominantly expressed in neuronal tissues. HK-1 has several biological activities that are similar to the most studied tachykinin, substance P, such as induction of plasma extravasation and mast cell degranulation. However, HK-1 also has properties that are indicative of a critical role in mouse B cell development. HK-1 stimulated the proliferation of interleukin 7-expanded B cell precursors, whereas substance P had no effect. HK-1, but not substance P, promoted the survival of freshly isolated bone marrow B lineage cells or cultured, lipopolysaccharide-stimulated pre-B cells. N-acetyl-L-trytophan-3,5-bistrifluromethyl benzyl ester, a tachykinin receptor antagonist, increased apoptosis of these cells and in vivo administration of this antagonist led to specific reductions of the B220lowCD43 population (the pre-B cell compartment) in the bone marrow and the IgMhighIgDlow population (the newly generated B cells) in the spleen. Thus, HK-1 may be an autocrine factor that is important for the survival of B cell precursors at a critical phase of development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • Base Sequence
  • Cell Division / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Cloning, Molecular
  • DNA Primers / genetics
  • DNA, Complementary / genetics
  • Hematopoiesis / drug effects
  • Humans
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Molecular Sequence Data
  • Protein Precursors / genetics*
  • Protein Precursors / immunology*
  • Protein Precursors / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Homology, Amino Acid
  • Tachykinins / genetics*
  • Tachykinins / immunology*
  • Tachykinins / pharmacology
  • Tryptophan / analogs & derivatives*
  • Tryptophan / pharmacology

Substances

  • DNA Primers
  • DNA, Complementary
  • Protein Precursors
  • RNA, Messenger
  • TAC4 protein, human
  • Tac4 protein, mouse
  • Tachykinins
  • preprotachykinin
  • 3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan
  • Tryptophan