Actions of the chemotactic cytokines MCP-1, MCP-2, MCP-3, RANTES, MIP-1 alpha and MIP-1 beta on human monocytes

Eur J Immunol. 1995 Jan;25(1):64-8. doi: 10.1002/eji.1830250113.

Abstract

The activities of six synthetic CC chemokines, MCP-1, MCP-2, MCP-3, RANTES, MIP-1 alpha and MIP-1 beta on human blood monocytes were studied. All CC chemokines elicited a bimodal migration response in vitro. Highest numbers of migrating cells were obtained with the monocyte chemotactic proteins (MCP) and RANTES, somewhat lower numbers with MIP-1 alpha, and only weak migration with MIP-1 beta. The most potent attractants were MCP-1 and MIP-1 alpha which reached maximum efficacy at 0.1 to 1 nM. All CC chemokines also induced the release of N-acetyl-beta-D-glucosaminidase from cytochalasin B-pretreated monocytes. The MCP were most effective (MCP-1 > MCP-3 > MCP-2), RANTES and MIP-1 alpha showed moderate (1/3 of MCP-1 activity), and MIP-1 beta only minimal activity. Cytosolic free Ca2+ changes and exocytosis were used to monitor receptor desensitization. Marked cross-desensitization was observed among MCP-1, MCP-2 and MCP-3 on the one hand, and RANTES, MIP-1 alpha and MIP-1 beta on the other, indicating receptor sharing within these two subgroups of CC chemokines. The responses to RANTES, MIP-1 alpha and MIP-1 beta were also moderately to markedly desensitized by pretreatment with MCP-1, MCP-2 or MCP-3, while the responses to the MCP were virtually unaffected by pretreatment with RANTES, MIP-1 alpha and MIP-1 beta. These results suggest that the MCP also interact with receptors recognized by RANTES, MIP-1 alpha and MIP-1 beta, but not vice versa. Binding studies were performed with radiolabeled MCP-1 or MIP-1 alpha. All MCP competed readily for labeled MCP-1 yielding a concentration-dependent sigmoidal displacement curve. Displacement with RANTES, MIP-1 alpha and MIP-1 beta was observed at higher concentrations, but was not complete. Radiolabeled MIP-1 alpha was displaced efficiently by MIP-1 alpha or MIP-1 beta, but only partially by RANTES. Of the MCP, only MC-3 completely displaced MIP-1 alpha, while only partial displacement was observed with MCP-1 and MCP-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosaminidase / metabolism
  • Calcium / metabolism
  • Chemokine CCL2
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokine CCL7
  • Chemokine CCL8
  • Chemotactic Factors / physiology*
  • Chemotaxis, Leukocyte / physiology*
  • Cytokines / physiology*
  • Exocytosis / physiology
  • Humans
  • In Vitro Techniques
  • Lymphokines / physiology
  • Macrophage Inflammatory Proteins
  • Monocyte Chemoattractant Proteins*
  • Monocytes / physiology*
  • Monokines / physiology
  • Protein Binding / physiology

Substances

  • CCL7 protein, human
  • CCL8 protein, human
  • Chemokine CCL2
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokine CCL7
  • Chemokine CCL8
  • Chemotactic Factors
  • Cytokines
  • Lymphokines
  • Macrophage Inflammatory Proteins
  • Monocyte Chemoattractant Proteins
  • Monokines
  • Acetylglucosaminidase
  • Calcium