Monocyte IL-8 release is induced by two independent Fc gamma R- mediated pathways.
Cross-linking of PBMC and monocyte Fc gamma R on immobilized IgG stimulates IL-8 release. We used immobilized anti-Fc gamma R Abs to determine which of the three surface Fc gamma R regulated this IL-8 secretion. Fc gamma RIII cross-linking stimulated PBMC to release 5 times more IL-8 than did either Fc gamma RI or Fc gamma RII clustering (p = 0.001) and stimulated 77% more IL-8 release from PBMC than that from purified monocytes (p = 0.001). In contrast, only Fc gamma RI cross-linking significantly induced monocytes to release IL-8 (p = 0.05). Since purified lymphocytes release little IL-8 in response to immobilized IgG or anti-Fc gamma RIII Abs, we hypothesized that lymphocyte Fc gamma R cross-linking augmented monocyte IL-8 release. Supernatants from IgG- or Fc gamma RIII -stimulated lymphocytes induced monocytes to release more IL-8 than lymphocytes incubated on plastic alone (p = 0.002 and p = 0.003, respectively). THP-1 cells, which do not produce IL-8 in response to Fc gamma i]R cross-linking, also released IL-8 in response to supernatants from IgG- or Fc gamma RIII-stimulated lymphocytes, suggesting that the supernatant activity was not soluble immune complexes. The IL-8-stimulating activity was heat labile, suggesting that the activity is a protein. However, we could not reproduce or block this activity using recombinant cytokines or neutralizing anti-cytokine Abs. Thus, monocyte IL-8 is stimulated directly through Fc gamma RI cross-linking and indirectly through an Fc gamma RIII-stimulated soluble lymphocyte factor.
Marsh
C B
CB
Division of Pulmonary and Critical Care Medicine, Ohio State University, Columbus 43210, USA.
Anderson
C L
CL
Lowe
M P
MP
Wewers
M D
MD
D003432:Cross-Linking Reagents; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D008222:Lymphokines / Q000737:chemistry / Q000276:immunology / Q000502:physiology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D017452:Receptors, IgG / Q000502:physiology*
D003432:Cross-Linking Reagents; D007074:Immunoglobulin G; D016209:Interleukin-8; D008222:Lymphokines; D017452:Receptors, IgG