Complement protein C1q modulates macrophage activation and inflammasome activity during the uptake of apoptotic cells. Homo sapiens

In this study, we developed a unique system using primary human autologous lymphocytes and HMDMs to characterize the effect of C1q on macrophage gene expression profiles during the uptake of apoptotic cells. Our results showed that C1q bound to autologous apoptotic lymphocytes (AL) significantly modulated the response of HMDMs to LPS by increasing expression of cytokines, chemokines and effector molecules associated with immunoregulation and by directly suppressing caspase-1 dependent cleavage of IL-1beta. Overall design: Human monocyte-derived macrophages (HMDMs) were incubated with early apoptotic lymphocytes (EAL), late apoptotic lymphocytes (LAL), C1q-EAL and C1q-LAL for 1h and then and stimulated with 10 ng/ml ultra-pure LPS. After 3 h of LPS stimulation, total RNA was extracted using the Illustra RNAspin Mini Isolation Kit. Gene expression profiles were studied using the Human Gene 1.0 ST array (Affymetrix). Slides were scanned using the Affymetrix GCOS software (performed by the microarray core facility at University of California, Irvine). Data processing and analysis were performed using JMP Genomics 5.0 software (SAS Institue Inc.). Significant differences in gene expression compared to unstimulated HMDMs were identified by ANOVA test using Holm multiple testing method and a false positive rate (alpha error) of 0.05