C1q-mediated chemotaxis by human neutrophils: involvement of gClqR and G-protein signalling mechanisms

Biochem J. 1998 Feb 15;330 ( Pt 1)(Pt 1):247-54. doi: 10.1042/bj3300247.

Abstract

C1q, the first component of the classical pathway of the complement system, interacts with various cell types and triggers a variety of cell-specific cellular responses, such as oxidative burst, chemotaxis, phagocytosis, etc. Different biological responses are attributed to the interaction of C1q with more than one putative cell-surface C1q receptor/C1q-binding protein. Previously, it has been shown that C1q-mediated oxidative burst by neutrophils is not linked to G-protein-coupled fMet-Leu-Phe-mediated response. In the present study, we have investigated neutrophil migration brought about by C1q and tried to identify the signal-transduction pathways involved in the chemotactic response. We found that C1q stimulated neutrophil migration in a dose-dependent manner, primarily by enhancing chemotaxis (directed movement) rather than chemokinesis (random movement). This C1q-induced chemotaxis could be abolished by an inhibitor of G-proteins (pertussis toxin) and PtdIns(3,4,5)P3 kinase (wortmannin and LY294002). The collagen tail of C1q appeared to mediate chemotaxis. gC1qR, a C1q-binding protein, has recently been reported to participate in C1q-mediated chemotaxis of murine mast cells and human eosinophils. We observed that gC1qR enhanced binding of free C1q to adherent neutrophils and promoted C1q-mediated chemotaxis of neutrophils by nearly seven-fold. Our results suggests C1q-mediated chemotaxis involves gC1qR as well as G-protein-coupled signal-transduction mechanisms operating downstream to neutrophil chemotaxis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Carrier Proteins
  • Chemotaxis, Leukocyte* / drug effects
  • Chromones / pharmacology
  • Collagen / chemistry
  • Complement C1q / physiology*
  • Enzyme Inhibitors / pharmacology
  • GTP-Binding Proteins / physiology*
  • Humans
  • Hyaluronan Receptors*
  • Membrane Glycoproteins*
  • Mitochondrial Proteins
  • Morpholines / pharmacology
  • Neutrophils / physiology*
  • Pertussis Toxin
  • Phosphoinositide-3 Kinase Inhibitors
  • Receptors, Complement / physiology*
  • Signal Transduction
  • Virulence Factors, Bordetella / pharmacology
  • Wortmannin

Substances

  • Androstadienes
  • C1QBP protein, human
  • Carrier Proteins
  • Chromones
  • Enzyme Inhibitors
  • Hyaluronan Receptors
  • Membrane Glycoproteins
  • Mitochondrial Proteins
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Receptors, Complement
  • Virulence Factors, Bordetella
  • complement 1q receptor
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Complement C1q
  • Collagen
  • Pertussis Toxin
  • GTP-Binding Proteins
  • Wortmannin