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Chemokines are secreted by monocytes following OK-432 (lyophilized Streptococcus pyogenes) stimulation

Carla Olsnes1, Helen Stavang, Karl Brokstad

  • 1Department of Surgical Sciences, Faculty of Medicine, University of Bergen, Bergen, Norway. carla.olsnes@ore.uib.no

BMC Immunology
|January 30, 2009
PubMed
Abstract

Insights

OK-432 stimulates adherent monocytes (MOs) to release immune-signaling chemokines like MCP-1 and MIP-1alpha/beta. This interaction, partly mediated by CD36, explains OK-432

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • OK-432, derived from Streptococcus pyogenes, is clinically used for lymphangiomas and carcinomas.
  • Mononuclear phagocytes (MNPs), including monocytes (MOs), play a role in immune responses.
  • Understanding MNP interaction with OK-432 is crucial for its therapeutic application.

Purpose of the Study:

  • To investigate the in vitro immune response of MNPs to OK-432.
  • To assess the secretion of chemokines (MIP-1alpha/beta, MCP-1) by MOs upon OK-432 stimulation.
  • To elucidate the mechanisms of MNP activation by OK-432, including adherence and specific receptors.

Main Methods:

  • In vitro stimulation of whole blood (WB), PBMCs, and purified MOs with OK-432.
  • Assessment of MIP-1alpha/beta and MCP-1 chemokine secretion.
  • Evaluation of the role of adherence, Syk kinase, PI-3 kinase, and integrins (beta1, beta3, beta2) in the response.
  • Investigation of CD36 and CD18 involvement via antibody blockage.

Main Results:

  • OK-432 induced MCP-1 and MIP-1alpha/beta secretion from MNPs in healthy individuals and HNSCC patients.
  • Minimal MIP-1alpha/beta response was observed upon OK-432 stimulation of whole blood.
  • Adherent MOs showed increased chemokine secretion upon OK-432 stimulation, partly mediated by CD36 and CD18.
  • Syk and PI-3 kinase inhibition showed varied effects on chemokine production.

Conclusions:

  • Adherent human MOs are key producers of MCP-1 and MIP-1alpha/beta in response to OK-432.
  • The CD36 receptor plays a role in modulating MIP-1beta and MCP-1 secretion.
  • OK-432's ability to elicit chemokine release primarily from adhered MOs contributes to its efficacy as a biological response modifying drug.

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