TY - JOUR
T1 - Effects of the physico-chemical nature of two biomimetic crystals on the innate immune response
AU - Ramesh, Manish
AU - Turner, Laura F.
AU - Yadav, Rajwardhan
AU - Rajan, Thiruchandurai V.
AU - Vella, Anthony T.
AU - Kuhn, Liisa T.
N1 - Funding Information:
The authors would like to acknowledge the Central Electron Microscopy facility at the University of Connecticut Health Center for the TEM micrographs. This work was made possible by NIAID grant awards AI 39705 and AI 42362 (T.V.R); AI 42858 and AI56172 (A.T.V); and University of Connecticut Health Center Institutional funds (L.T.K).
PY - 2007/12/15
Y1 - 2007/12/15
N2 - The influence of the physico-chemical features of particulates made of calcium phosphate (hydroxyapatite, HAP) crystals, or monosodium urate monohydrate (MSUM) crystals, on the innate immune response was investigated in mice after intraperitoneal injections. The phenotype and activation status of harvested peritoneal cells from C57BL/6 mice was determined by flow cytometry analysis at 24, 48 and 72 h after particulate injections and compared to a known adjuvant, aluminum phosphate (ALP). A rigorous characterization of the chemistry, structure, morphology and particle size of the particulates was completed. Mid-sized (10 μm mean size) particulates of both crystal types recruited the most cells, as compared to fine (1 μm) or large (100 μm) particulates. Analysis of sub-populations of the peritoneal cells revealed that MSUM induced fewer PMNs and eosinophils than HAP or ALP. MSUM also had the greatest effect on the expression of CD11b, MHC-Class II and CD86 on peritoneal macrophages indicating MSUM provides a robust antigen presenting and co-stimulatory bridge between the innate and adaptive immune systems. This study indicates that manipulation of the physico-chemical features of particulates is a means of controlling the innate immune response and that knife-like morphologies are more stimulatory than spherical or plate-like shapes. Proper utilization of the physico-chemical features of particulates offers a new direction for the development of more effective vaccine adjuvants.
AB - The influence of the physico-chemical features of particulates made of calcium phosphate (hydroxyapatite, HAP) crystals, or monosodium urate monohydrate (MSUM) crystals, on the innate immune response was investigated in mice after intraperitoneal injections. The phenotype and activation status of harvested peritoneal cells from C57BL/6 mice was determined by flow cytometry analysis at 24, 48 and 72 h after particulate injections and compared to a known adjuvant, aluminum phosphate (ALP). A rigorous characterization of the chemistry, structure, morphology and particle size of the particulates was completed. Mid-sized (10 μm mean size) particulates of both crystal types recruited the most cells, as compared to fine (1 μm) or large (100 μm) particulates. Analysis of sub-populations of the peritoneal cells revealed that MSUM induced fewer PMNs and eosinophils than HAP or ALP. MSUM also had the greatest effect on the expression of CD11b, MHC-Class II and CD86 on peritoneal macrophages indicating MSUM provides a robust antigen presenting and co-stimulatory bridge between the innate and adaptive immune systems. This study indicates that manipulation of the physico-chemical features of particulates is a means of controlling the innate immune response and that knife-like morphologies are more stimulatory than spherical or plate-like shapes. Proper utilization of the physico-chemical features of particulates offers a new direction for the development of more effective vaccine adjuvants.
KW - Hydroxyapatite
KW - Inflammation
KW - Innate immune response
KW - Monosodium urate monohydrate
KW - Particulate adjuvant
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U2 - 10.1016/j.intimp.2007.08.011
DO - 10.1016/j.intimp.2007.08.011
M3 - Article
C2 - 17996671
AN - SCOPUS:35748932672
SN - 1567-5769
VL - 7
SP - 1617
EP - 1629
JO - International Immunopharmacology
JF - International Immunopharmacology
IS - 13
ER -
