Objective. To investigate whether monocyte chemotactic and activating factor (MCAF) contributes to the accumulation of macrophages in the joints of patients with rheumatoid arthritis (RA). Methods. MCAF was measured by radioimmunoassay. MCAF gene expression was determined by Northern blotting and reverse‐transcriptase polymerase chain reaction. Recombinant human MCAF was injected into rabbit joints to evaluate the effect of MCAF on infiltration of macrophages. Results. High levels of MCAF were detected in synovial fluid from patients with RA. Cells freshly isolated from synovial fluid expressed MCAF messenger RNA (mRNA). Fibroblast‐like synoviocytes were found to express MCAF mRNA and to secrete MCAF in response to interleukin‐1 (IL‐1) and tumor necrosis factor in vitro. IL‐1 also promoted MCAF gene expression in rabbit synovial tissue in vivo. MCAF caused marked infiltration of macrophages in rabbit synovial tissue. Conclusion. Our findings suggest that MCAF may contribute to the accumulation of macrophages in inflamed rheumatoid joints.

The present study suggests that calprotectin expression is related to keratinocyte differentiation and that C/EBPalpha is a regulator of calprotectin expression in keratinocytes.

The infiltration of leucocytes into the joint of rheumatoid arthritis (RA) is believed to be mediated by chemotactic factors released by activated cells. In this study, examination was made of the gene expression and production of the chemokine superfamily in RA patients by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoprecipitation. Cultured synovial fibroblasts were found capable of expressing and producing IL-8, GRO, monocyte chemotactic and activating factor (MCAF), macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta and RANTES in response to IL-1 alpha. The expression of IL-8, GRO, MCAF, MIP-1 alpha, and MIP-1 beta was clearly shown to increase in freshly isolated synovial fluid mononuclear cells (SFMC) of RA patients, in contrast to peripheral blood mononuclear cells (PBMC) of RA patients and normal subjects. The gene expression of RANTES appeared to be the same for RA SFMC, RA PBMC, and normal PBMC. Thus, the over-expression of various chemokines may promote the recruitment of inflammatory cells into rheumatoid inflamed joints.

Tumorigenesis has been shown to proceed through a series of genetic alterations involving protooncogenes and tumor-suppressor genes. Investigation of genomic instability of microsatellites has indicated a new mechanism for human carcinogenesis in hereditary nonpolyposis colorectal cancer and sporadic cancer and this instability has been shown to be related to inherited predisposition to cancer. This study was conducted to determine whether such microsatellite instability is associated with the evolution of chronic myelogenous leukemia (CML) to the blast crisis. Nineteen CML patients clinically progressing from the chronic phase to accelerated phase or blast crisis and 20 other patients in the CML chronic phase were studied. By polymerase chain reaction assay, DNAs for genomic instability in five separate microsatellites in chromosome arms 5q (Mfd27), 17p (Mfd41), 18q (DCC), 3p (CI3–9), and 8p (LPL) were examined. Differences in unrelated microsatellites of chronic and blastic phase DNAs in 14 of 19 patients (73.7%) were demonstrated. Somatic instability in five microsatellites, Mfd27, Mfd41, DCC, CI3–9, and LPL, was detected in 2 of 19 (10.5%), 8 of 19 (42.1%), 11 of 19 (57.9%), 4 of 17 (23.5%), and 4 of 17 (23.5%) cases. In 10 of 19 cases (52.6%), genetic instability in at least two of five microsatellites was observed and was categorized as replication error (RER+) phenotype. CML evolution cases with myeloid, lymphoid, and mixed phenotypes and the blast crisis and accelerated phase showed somatic instability in a number of microsatellites. No alterations in leukemic cells at the chronic phase could be detected in any microsatellites. These data indicate instability of microsatellites (RER+) but not familial predisposition to possibly be a late genetic event in the evolution of CML to blast crisis. In the microsatellite of the DCC gene, complicated alterations in band patterns caused by instability as well as loss of heterozygosity (LOH) were observed in 13 of 19 cases (68.4%): instability in 9 cases, instability plus LOH in 2 cases, and only LOH in 2 cases. These highly frequent alterations in microsatellites, including instability and LOH, suggesting that secondary events due possibly to loss of fidelity in replication and repair machinery may be significantly associated with CML evolution.