Immune complex size and complement regulate cytokine production by peripheral blood mononuclear cells.
We have previously shown that immune complexes isolated from children with juvenile rheumatoid arthritis are heterogeneous in their size, composition, and proinflammatory capacities. The experiments described here were undertaken to clarify further the roles of size and composition in determining the proinflammatory effects of immune complexes. We incubated peripheral blood mononuclear cells (PBMCs) with different soluble immune complex preparations: opsonized complexes, which were formed in the presence of serum, unopsonized complexes, which were formed in the absence of serum, and immune precipitates solubilized by complement after their formation. ELISA assays showed that immune complexes formed in the presence of complement were less efficient than unopsonized complexes in inducing IL-1beta and IL-8 secretion from leukocytes. Solubilized immune precipitates showed intermediate capacity to stimulate the release of both cytokines. Complexes formed in heat-inactivated serum were as efficient as unopsonized complexes in eliciting cytokine secretion from the cells. The capacity of complement to regulate cytokine secretion from leukocytes was related, at least in part, to immune complex size. Sucrose density gradients showed unopsonized complexes and solubilized immune precipitates were larger than opsonized immune complexes. In contrast, fluid-phase binding of C4 to immune complexes, which did not appreciably change immune complex size, substantially increased IL-1beta secretion from PBMC.
Jarvis
J N
JN
Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma 73013, USA. james-jarvis@ouhsc.edu
Xu
C
C
Wang
W
W
Petty
H R
HR
Gonzalez
M
M
Morssy
N
N
Waxman
F
F
Quintero del Rio
A
A
D000936:Antigen-Antibody Complex / Q000737:chemistry* / Q000378:metabolism; D015152:Blotting, Northern; D003181:Complement C4 / Q000378:metabolism; D015935:Complement C4b; D003165:Complement System Proteins / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D009895:Opsonin Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D015203:Reproducibility of Results; D012995:Solubility
D000936:Antigen-Antibody Complex; D003181:Complement C4; D007375:Interleukin-1; D016209:Interleukin-8; D009895:Opsonin Proteins; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d; D003165:Complement System Proteins