PMID:11062498

Citation	Zhang, Y, Lu, L, Furlonger, C, Wu, GE and Paige, CJ (2000) Hemokinin is a hematopoietic-specific tachykinin that regulates B lymphopoiesis. Nat. Immunol. 1:392-7
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.
Links	PubMed Online version:10.1038/80826
Keywords	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; 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
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