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Hemokinin is a hematopoietic-specific tachykinin that regulates B lymphopoiesis

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.

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Figure 1: Sequences of PPT-C and HK-1.
Figure 2: Expression of the Pptc gene.
Figure 3: Decreased expression of PPT-C in, and protective effect of HK-1 on,70Z/3 following LPS stimulation.
Figure 4: Enhanced survival and proliferation of primary B lineage cells by HK-1.
Figure 5: FACS analysis of bone marrow and spleen cells from tachykinin antagonist–treated mice.

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Acknowledgements

Supported by the National Cancer Institute of Canada with funds from the Terry Fox Foundation, and the Canadian Institutes for Health Research.

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Correspondence to Christopher J. Paige.

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Zhang, Y., Lu, L., Furlonger, C. et al. Hemokinin is a hematopoietic-specific tachykinin that regulates B lymphopoiesis . Nat Immunol 1, 392–397 (2000). https://doi.org/10.1038/80826

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