Anti-apoptotic effect of nerve growth factor is lost in congenital insensitivity to pain with anhidrosis (CIPA) B lymphocytes

J Clin Immunol. 2004 May;24(3):302-8. doi: 10.1023/B:JOCI.0000025452.79585.a1.

Abstract

Congenital insensitivity to pain with anhidrosis (CIPA) is identified as a genetic disorder of mutations in the human TrkA known as high affinity receptor of nerve growth factor (NGF). NGF signal through TrkA promotes anti-apoptotic activity in hematopoietic cells including B lymphocytes. Here we studied the effect of NGF on anti-apoptotic activity by using human EBV-immortalized B lymphoblastoid cell lines (EB-LCLs) derived from a patient with CIPA and the associated carriers of CIPA. The TrkA(mt/mt) EB-LCL derived from the CIPA patient and the TrkA(wt/mt) EB-LCL derived from the carrier with the heterozygous TrkA mutation did not show any responses to NGF on anti-apoptotic activity. We concluded that this phenomenon is one of the pathogeneses of CIPA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins
  • Apoptosis* / physiology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism
  • Bcl-2-Like Protein 11
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Female
  • Gliotoxin / pharmacology
  • Hereditary Sensory and Autonomic Neuropathies / genetics
  • Hereditary Sensory and Autonomic Neuropathies / metabolism*
  • Hereditary Sensory and Autonomic Neuropathies / pathology
  • Humans
  • Infant
  • Membrane Proteins / metabolism
  • Nerve Growth Factor / pharmacology*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptor, trkA / genetics*
  • Receptor, trkA / physiology
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • BCL2L1 protein, human
  • BCL2L11 protein, human
  • Bcl-2-Like Protein 11
  • Carrier Proteins
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • Gliotoxin
  • Nerve Growth Factor
  • Receptor, trkA
  • p38 Mitogen-Activated Protein Kinases