Modulation of the mRNAs encoding substance P and its receptor in rat macrophages by LPS

Reg Immunol. Mar-Apr 1992;4(2):105-12.

Abstract

Numerous soluble factors and their receptors contribute to the regulation of immune responses. An important area of investigation concerns defining the regulation of expression of such receptor/ligand pairs, since understanding such events are central in the quest to manipulate immune responses. Receptors for the neuropeptide, substance P, are present on a variety of leukocytes, and these receptor positive cells respond to in vitro stimulation with substance P in a variety of ways. Unfortunately, little is known about the regulation of expression of substance P or its receptor in leukocytes. Here we begin to address this question by examining the ability of macrophages to express mRNAs which encode substance P and its receptor. A radiolabeled oligonucleotide probe complementary to the mRNA which encodes substance P (i.e., preprotachykinin mRNA) hybridized to a 1.3 kb RNA species present in rat macrophages. In addition, the expression of this RNA could be upregulated 6 to 8 fold when macrophages were stimulated with LPS. The ability of macrophages to synthesize and secrete immunoreactive-substance P was demonstrated by incorporation of L-[35S]methionine into material from macrophage cultures which could be recognized by a monoclonal antisubstance antibody. Macrophage RNA of approximately 3.1 kb in size was capable of hybridizing with an oligonucleotide probe complementary to rat brain substance P receptors. In addition, this RNA could be upregulated when cells were exposed to LPS. Taken together, these studies suggest that the genes used by neuronal cells and macrophages to encode substance P and its receptor are similar if not identical.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Endotoxins / pharmacology*
  • Female
  • Leukemia P388 / genetics
  • Leukemia P388 / metabolism
  • Leukemia P388 / pathology
  • Lipopolysaccharides*
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Molecular Sequence Data
  • Neuroimmunomodulation*
  • Protein Precursors / genetics
  • RNA Processing, Post-Transcriptional / drug effects*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA, Neoplasm / genetics
  • Rats
  • Rats, Inbred Strains
  • Receptors, Neurokinin-1
  • Receptors, Neurotransmitter / genetics*
  • Substance P / genetics*
  • Substance P / metabolism
  • Tachykinins / genetics

Substances

  • Endotoxins
  • Lipopolysaccharides
  • Protein Precursors
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Neurokinin-1
  • Receptors, Neurotransmitter
  • Tachykinins
  • preprotachykinin
  • Substance P