Superoxide release by peritoneal and bone marrow-derived mouse macrophages. Modulation by adherence and cell activation.
Macrophages (M phi) activated by BCG and other immune stimuli differ from thioglycollate-elicited M phi (TPM) in releasing O-2 upon initial contact with a foreign substratum. During adherence and spreading, activated M phi release approximately 50% of O-2 levels triggered by phorbol myristate acetate (PMA). The response requires divalent cations (Ca++ or Mg++) and is sensitive to lignocaine, a reversible inhibitor of adhesion. These features distinguish this reaction from the response to PMA, which also triggers substantial release of O-2 from TPM, 60-80% of bacille Calmette--Guérin-activated peritoneal M phi (BCG-PM) activity. During prolonged cultivation as monolayers, peritoneal and bone marrow derived M phi (BMDM) progressively lose their ability to release O-2 in response to PMA and serum-treated zymosan (STZ), although the cells continue to secrete other products and to phagocytose STZ. This loss can be prevented by maintaining peritoneal and BMDM as non-adherent cells in teflon beakers or poly-(2-hydroxyethylmethacrylate) (poly HEMA) coated vessels. High levels of O-2 activity were observed after cultivating TPM on poly-HEMA (300 nmoles O-2/mg/hr after PMA), 10-fold more than adherent controls. BMDM could be induced to release four-fold more O-2, greater than 100 nmoles O-2/mg/hr, after cultivation as non-adherent cells in the absence of L cell-conditioned medium. Our results show that heterogeneity in M phi respiratory burst activity depends on (i) intrinsic differences between populations, (ii) differential responses by activated and non-activated M phi to selective surface stimuli and (iii) modulation by environmental factors which control adherence and growth.
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D001854:Bone Marrow Cells; D002448:Cell Adhesion; D002478:Cells, Cultured; D005260:Female; D008012:Lidocaine / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008689:Methacrylates; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D008689:Methacrylates; D013481:Superoxides; C005044:hydroxyethyl methacrylate; D015054:Zymosan; D008012:Lidocaine; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen