A Homologous Form of Human Interleukin 16 Is Implicated in Microglia Recruitment Following Nervous System Injury in Leech Hirudo Medicinalis

Glia. 2010 Nov 1;58(14):1649-62. doi: 10.1002/glia.21036.

Abstract

In contrast to mammals, the medicinal leech Hirudo medicinalis can completely repair its central nervous system (CNS) after injury. This invertebrate model offers unique opportunities to study the molecular and cellular basis of the CNS repair processes. When the leech CNS is injured, microglial cells migrate and accumulate at the site of lesion, a phenomenon known to be essential for the usual sprouting of injured axons. In the present study, we demonstrate that a new molecule, designated HmIL-16, having functional homologies with human interleukin-16 (IL-16), has chemotactic activity on leech microglial cells as observed using a gradient of human IL-16. Preincubation of microglial cells either with an anti-human IL-16 antibody or with anti-HmIL-16 antibody significantly reduced microglia migration induced by leech-conditioned medium. Functional homology was demonstrated further by the ability of HmIL-16 to promote human CD4+ T cell migration which was inhibited by antibody against human IL-16, an IL-16 antagonist peptide or soluble CD4. Immunohistochemistry of leech CNS indicates that HmIL-16 protein present in the neurons is rapidly transported and stored along the axonal processes to promote the recruitment of microglial cells to the injured axons. To our knowledge, this is the first identification of a functional interleukin-16 homologue in invertebrate CNS. The ability of HmIL-16 to recruit microglial cells to sites of CNS injury suggests a role for HmIL-16 in the crosstalk between neurons and microglia in the leech CNS repair.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / physiology*
  • Cells, Cultured
  • Disease Models, Animal
  • Ganglia, Invertebrate / cytology*
  • Ganglia, Invertebrate / injuries*
  • Ganglia, Invertebrate / physiology
  • Hirudo medicinalis / cytology*
  • Hirudo medicinalis / physiology*
  • Humans
  • Interleukin-16 / antagonists & inhibitors
  • Interleukin-16 / physiology*
  • Microglia / cytology
  • Microglia / physiology*
  • Sequence Homology, Amino Acid*

Substances

  • Interleukin-16