The experimental validation of the advantages of combined emergency (fluoroquinolones) and specific (EV Nalr) prevention of plague versus their sequential use]

Mice immunization with reference vaccine at the early stage of plague infection provided animals survival and prolonged mean survival period up to 2-5 days. Ciprofloxacin, ofloxacin and pefloxacin prevents development of post vaccine immunity at white mice, immunized by reference vaccine strain EV. Nalidixic acid and norfloxacin effect on post vaccine immunity was lower. Use of immunogenic strain EV Nafr (resistant to nalidixic acid and fluoroquinolones) provided antiplague immunity formation at the background of fluoroquinolones prophylaxis. Ciprofloxacin, ofloxacin and pefloxacin used for plague prophylaxis at white mice infected with Yersinia pestis (about 1000 LD50) inhibited postinfective immunity development. Nalidixic acid and norfloxacin didn't demonstrate such effect. Urgent (fluoroquinolones) and specific (EV Nalr) combined prophylaxis was evaluated as more effective for a 5-day period and provided the development of antiplague immunity.     

Effect of glycosylation inhibitors on binding properties of the Fc gamma receptors from guinea pig peritoneal macrophages.

Guinea pig peritoneal macrophages possess on their surfaces receptors for the Fc region of IgG immunoglobulins (Fc gamma R). The cells treated with the glycosylation inhibitors tunicamycin or monensin interacted with IgG with a higher affinity and showed a lower number of IgG-binding sites in comparison with control cells. This indicates that the interaction of IgG with the macrophage Fc gamma receptor depends on the degree of glycosylation of the cell surface glycoconjugates and that glycosylation of the macrophage Fc gamma receptor is important for the expression of the mature form of the receptor.     

Pharmacologic evidence for the requirement of protein kinase C in IFN-induced macrophage Fc gamma receptor and Ia antigen expression.

Previous studies have implicated protein kinase C (PKC) as a mediator in the activation of macrophages by interferons. In order to probe further into the suspected role of protein kinase C in mouse peritoneal macrophage activation, the effects of protein kinase inhibitors in macrophage Fc gamma R and Ia Ag expression were studied. The protein kinase inhibitor, H7, reduced basal levels, and inhibited IFN-alpha-induced expression of Fc gamma R significantly. The concentration of H7 required to inhibit 50% of the Fc gamma R induction was approximately 12 microM, which reflects the previously reported affinity of this compound for PKC in vitro. H7 had only a minimal effect on IFN-gamma-induced Fc gamma R, suggesting different pathways of Fc gamma R induction by the two types of IFN. Ia induction by IFN-gamma was also inhibited by H7, indicating that both types of IFN can utilize PKC to mediate at least part of the signal required for Fc gamma R or Ia expression. HA-1004, a derivative of H7 which possesses high affinity for cyclic nucleotide-dependent protein kinases, but low affinity for PKC, did not alter induction, while H8, a slightly less effective PKC inhibitor than H7, was effective at higher concentrations. Another structurally distinct PKC antagonist, staurosporine, was also effective inhibiting IFN-alpha-induced Fc gamma R and IFN-gamma-induced Ia Ag expression, providing additional evidence that PKC is important. H7 was found to be effective when added as late as several hours after IFN treatment, indicating a prolonged or delayed requirement of PKC for optimal induction of Ia and Fc gamma R by IFN.     

Evaluation of outcomes of combined specific prophylaxis with the antibiotic resistant immunogenic plague pathogen strain and emergency prophylaxis with aminoglycosides in the experimental plague model in white mice]

It was shown that aminoglycosides (streptomycin, kanamycin, gentamicin, sisomicin, tobramycin, amikacin) prevented manifestation of postvaccine immunity in albino mice immunized by vaccine strain Yersinia pestis EV. Avirulent strain Y. pestis 363 Monr with chromosome resistance to aminoglycosides of the 1st, 2nd and 3rd generations provided manifestation of antiplague immunity when streptomycin, kanamycin, gentamicin and amikacin were administered for prophylaxis. ED50 achieved 1.0-1.2 x 10(3) CFU and in control group (without treatment) 9.3 x 10(2) CFU. Gentamicin and amikacin were highly effective for experimental plague prophylaxis (90-100% animal survival), but inhibited development of postinfective immunity. Protective index (PI) value was 1.1 x 10(2). It was demonstrated that combination of specific prophylaxis (Y. pestis 363 Monr) and emergency prophylaxis with aminoglycosides in albino mice infected with approximately 1000 LD50 of virulent strain Y. pestis 358 (5 hours after infection) was highly effective and provided protective effect against subsequent infection with plague pathogen. Value of PI was 1.1 x 10(5) and practically did not differ from PI (1.7 x 10(5)) in control group (intact mice, immunized with strains EV [symbol: see text] 363 Monr).     

Properties of a second epitope of the murine Fc receptor for aggregated IgG

The murine macrophage and lymphocyte Fc receptor for aggregated IgG (Fc gamma R) has previously been characterized by using the anti-Fc gamma R monoclonal antibody (mAb), 2.4G2. In the studies presented here, we describe a new mAb, 6B7C, that defines a second epitope of the Fc gamma R. The tissue distribution of the 6B7C epitope is coincident with the 2.4G2 epitope. However, only the 2.4G2 epitope is accessible to mAb binding on intact primary macrophages or lymphocytes. The 6B7C epitope is not detectable on primary macrophages or lymphocytes but is exposed on a portion of B lymphocyte Fc gamma R after activation by lipopolysaccharide and on some tumor cell lines. The expression of the 6B7C epitope on the surface of B lymphoblasts and tumor cell lines seems to correlate with their ability to release soluble Fc gamma R. The 6B7C mAb has the advantage that it reacts with native as well as denatured receptor and therefore can be used for techniques such as immunoblotting.     

The inositol 3-phosphatase PTEN negatively regulates Fc gamma receptor signaling, but supports Toll-like receptor 4 signaling in murine peritoneal macrophages

Fc gamma R clustering in macrophages activates signaling events that result in phagocytosis. Phagocytosis is accompanied by the generation harmful byproducts such as reactive oxygen radicals and production of inflammatory cytokines, which mandate that the phagocytic process be subject to a tight regulation. The molecular mechanisms involved in this regulation are not fully understood. In this study, we have examined the role of the inositol 3-phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in Fc gamma R-induced macrophage function. We demonstrate that in ex vivo murine peritoneal macrophages that are deficient in PTEN expression, Fc gamma R-induced Akt and extracellular signal-regulated kinase phosphorylation are enhanced. Notably, PTEN(-/-) macrophages showed constitutively high phosphorylation of Akt. However, PTEN did not seem to influence tyrosine phosphorylation events induced by Fc gamma R clustering. Furthermore, PTEN(-/-) macrophages displayed enhanced phagocytic ability. Likewise, Fc gamma R-induced production of TNF-alpha, IL-6, and IL-10 was significantly elevated in PTEN(-/-) macrophages. Surprisingly, LPS-induced TNF-alpha production was down-regulated in PTEN(-/-) macrophages. Analyzing the molecular events leading to PTEN influence on LPS/Toll-like receptor 4 (TLR4) signaling, we found that LPS-induced activation of mitogen-activated protein kinases is suppressed in PTEN(-/-) cells. Previous reports indicated that LPS-induced mitogen-activated protein kinase activation is down-regulated by phosphatidylinositol 3-kinase through the activation of Akt. Our observation that Akt activation is basally enhanced in PTEN(-/-) cells suggests that PTEN supports TLR4-induced inflammatory responses by suppressing the activation of Akt. Thus, we conclude that PTEN is a negative regulator of Fc gamma R signaling, but a positive regulator of TLR4 signaling. These findings are the first to demonstrate a role for PTEN in Fc gamma R- and TLR4-mediated macrophage inflammatory response.     

Effect of endogenous and synthetic sex steroids on the clearance of antibody-coated cells

Steroid hormones may influence the clinical expression of immunologic disease; however, their mechanism of action is uncertain. By using an experimental model, we studied the effect of sex steroids on the clearance of antibody-coated cells by macrophages in the spleen and liver. Progesterone significantly inhibited the clearance of IgG-coated E by splenic macrophages, whereas no effect was observed on the clearance of heat-altered E. This effect of progesterone was observed at serum concentrations which are attained during human pregnancy and the menstrual cycle. Furthermore, when splenic macrophages were isolated from progesterone-treated animals, they expressed decreased Fc gamma R activity. In addition, structural analogs of progesterone which have diminished glucocorticoid and progesterone activity retained this effect on macrophage Fc gamma R. In contrast, the estrogens estradiol and estriol as well as a structural estrogen analog with minimal estrogenic activity, 1,3,5(10)-estratrien-3,16 beta-diol, enhanced splenic macrophage Fc gamma R-dependent clearance. This action of estradiol could be partially inhibited by the antiestrogen tamoxifen. However, estradiol did not affect the C3-dependent clearance of IgM-coated E by hepatic macrophages. Concurrent administration of estradiol and progesterone demonstrated that the action of estradiol was predominant. These studies indicate that sex steroids alter splenic macrophage Fc gamma R function in vivo. This result may explain the alteration of disease activity in some human immunologic disorders during changes in hormonal state. Furthermore, analogs of progesterone and estrogen, as well as antiestrogens, which minimally affect the sex organs, retain the ability to alter splenic macrophage Fc gamma R function.     

L-FABP is exclusively expressed in alveolar macrophages within the myeloid lineage: evidence for a PPARalpha-independent expression

Peroxisome proliferator-activated receptors (PPARs) play a role in inflammation and, in particular, PPARgamma is involved in monocyte/macrophage differentiation. Members of the fatty acid-binding protein (FABP) family have been reported to function as transactivators for PPARs. Therefore, the expression of PPARs and FABPs in the myeloid lineage was investigated by real-time PCR and immunofluorescence analysis. We found adipocyte-, epidermal-, and heart-type FABP to be ubiquitously expressed within the myeloid lineage. In contrast, liver-type FABP was exclusively detected in murine alveolar macrophages (AM), confirmed on protein level by double fluorescence analysis. The PPAR subtypes also showed a temporally and spatially regulated expression pattern in myeloid cells: the beta-subtype was expressed in bone marrow, peritoneal, and alveolar macrophages, whereas it was not detected in dendritic cells (DCs). The gamma1-isoform was present in all cells, however, at different levels, whereas the gamma2-isoform was expressed in alveolar macrophages and dendritic cells. A low level PPARalpha mRNA could be detected in peritoneal macrophages and immature dendritic cells but not in mature dendritic cells and bone marrow macrophages. Interestingly, PPARalpha mRNA was also absent in the alveolar macrophages although liver-type FABP was expressed, indicating that gene expression of liver-type FABP was independent of PPARalpha. Since liver-type FABP is known as transactivator of PPARgamma the simultaneous expression of both proteins may have general implications for the activation of PPARgamma in alveolar macrophages.     

Further evidence for heterogeneity of Fc gamma-receptors on guinea pig splenic B and T lymphocytes: analysis using monoclonal antibodies to two distinct types of Fc gamma-receptor

In our previous paper, we reported that guinea pig splenic lymphocytes expressed two distinct Fc-receptors for homologous IgG (Fc gamma Rs), one monospecific for IgG2 (Fc gamma 2R) and the other bispecific for IgG1 and IgG2 (Fc gamma 1/gamma 2R), when analyzed by EA-rosette assay. These Fc gamma Rs on the cells were further studied by using two monoclonal antibodies toward the Fc gamma Rs on guinea pig peritoneal macrophages (anti-Fc gamma 1/gamma 2R and anti-Fc gamma 2R antibody). The anti-Fc gamma 1/gamma 2R antibody completely inhibited the rosette formation of splenic lymphocytes with IgG1-sensitized sheep erythrocytes [EA(IgG1)]. On the other hand, EA(IgG2)-rosette formation was inhibited partially by anti-Fc gamma 2R but not by anti-Fc gamma 1/gamma 2R antibody. Complete inhibition of the EA (IgG2)-rosette formation was achieved by simultaneous additions of both anti-Fc gamma 2R and anti-Fc gamma 1/gamma 2R antibodies. The binding of IgG2 antibody complexed with ovalbumin to the cells was partially inhibited by either anti-Fc gamma R antibody, and complete inhibition occurred in the presence of both the antibodies, indicating that two types of Fc gamma R, Fc gamma 1/gamma 2R, and Fc gamma 2R, are expressed on the cells. The determination of these Fc gamma Rs on B and T lymphocytes by two-color flow cytometry showed that about 52% of B lymphocytes expressed Fc gamma 1/gamma 2R alone and 32% of the cells expressed both the Fc gamma Rs. On the other hand, about 12% of T lymphocytes was found to express Fc gamma 2R alone and the cells expressing Fc gamma 1/gamma 2R were in the minority (3.8%). T lymphocytes expressing both the Fc gamma Rs were not detected. These results show that guinea pig B lymphocytes bear two types of Fc gamma Rs and are heterogeneous with regard to their Fc gamma Rs and that T lymphocytes express Fc gamma 2R mainly.     

Effect of recombinant IFN-gamma (rIFN-gamma) on the mechanism of human macrophage IgG FcRI-mediated cytotoxicity. rIFN-gamma decreases inhibition by cytophilic human IgG and changes the cytolytic mechanism.

Different classes of receptors for the Fc moiety of IgG (Fc gamma R) have been defined on human monocytes and macrophages: Fc gamma RI, Fc gamma RII, and Fc gamma RIII. All three classes are capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC). Fc gamma RI, which binds monomeric human IgG (hIgG) with high affinity, was shown an effective cytotoxic trigger molecule on different types of cells. In vitro, the inhibition of Fc gamma RI-mediated ADCC by hIgG is well documented. The low affinity receptor classes, Fc gamma RII and Fc gamma RIII, are not blocked by monomeric hIgG. Because monomeric hIgG is present at high concentrations in plasma and interstitial fluids it has been postulated inhibitory in vivo. We investigated the effect of rIFN-gamma on macrophage Fc gamma RI-mediated ADCC in the presence of low doses hIgG. With human E sensitized with hIgG as target cells, Fc gamma RI was studied selectively. We found that rIFN-gamma enhances both expression and cell surface density of Fc gamma RI on cultured peripheral blood monocytes. Furthermore, this cytokine partially reversed the inhibitory effect of monomeric hIgG on ADCC. More interestingly, we found that the cytolytic mechanism of monocyte-derived macrophages changed completely after prolonged culture with rIFN-gamma. Monocytes cultured for 9 days in control medium mediate predominantly phagocytosis. After long term rIFN-gamma stimulation (9 days), monocyte-derived macrophages almost completely lost the capacity to perform phagocytosis. Interestingly, they became highly efficient in mediating extracellular lysis of human E sensitized with hIgG. Short term rIFN-gamma stimulated monocyte-derived macrophages (for the last 40 h of culture) were found to mediate both phagocytosis and extracellular lysis. Our findings suggest that in vivo rIFN-gamma-stimulated macrophages may be most efficient in Fc gamma RI-mediated cytolysis as a consequence of a changed cytolytic mechanism in combination with enhanced Fc gamma RI density.     

The structure and expression of the guinea pig Fc receptor for IgG1 and IgG2 (Fc gamma 1/gamma 2R).

A cDNA clone encoding the receptor for guinea pig immunoglobulin G was isolated from a guinea pig peritoneal macrophage cDNA library. The cloned cDNA encoded 271 amino acids containing an N-terminal signal sequence. The deduced amino acid sequence is most homologous to murine Fc gamma RII beta 2. The receptor protein could be expressed in COS-7 and L cells transfected with the cDNA, suggesting that the expression of this receptor does not require the co-expression of a second chain such as gamma chain of Fc epsilon RI or CD3 zeta chain. The transformant L cells showed the binding to both the guinea pig IgG1 and IgG2 antibodies complexed with antigen, indicating that the cDNA we cloned was the one for guinea pig Fc gamma 1/gamma 2R.     

Experimental evaluation of prospects for the use of beta-lactams in plague infection caused by pathogens with plasmid resistance to penicillins]

High therapeutic efficacies of ceftriaxone, ceftazidime, cefotaxime and azthreonam in the treatment of experimental plague induced by beta-lactamase-producing strains of the plague microbe containing R plasmids RP-1, R57b and R40a were shown to correlate with their in vitro antibacterial activities. The therapeutic efficacy of sulbactam/ampicillin was recorded in the treatment of plague induced by the strain containing R plasmids R57b and R40a (the treatment course of 7 days). However, it was lower when the infection was due to the strain containing plasmid RP-1 (beta-lactamase TEM-2). Cefoperazone was not active in the treatment of experimental plague induced by the strains containing plasmids RP-1 and R57b (beta-lactamases TEM-2 and OXA-3). Ceftriaxone versus the antibiotics tested was considered to be the drug of choice for the etiotropic therapy of plague induced not only by the type strains of the plague microbe but also by its variants with the plasmid pattern resistance to penicillins.     

Fc gamma R expression on macrophages is related to severity and chronicity of synovial inflammation and cartilage destruction during experimental immune-complex-mediated arthritis (ICA)

STATEMENT OF FINDINGS: We investigated the role of Fc gamma receptors (Fc gamma Rs) on synovial macrophages in immune-complex-mediated arthritis (ICA). ICA elicited in knee joints of C57BL/6 mice caused a short-lasting, florid inflammation and reversible loss of proteoglycans (PGs), moderate chondrocyte death, and minor erosion of the cartilage. In contrast, when ICA was induced in knee joints of Fc receptor (FcR) gamma-chain(-/-) C57BL/6 mice, which lack functional Fc gamma RI and RIII, inflammation and cartilage destruction were prevented. When ICA was elicited in DBA/1 mice, a very severe, chronic inflammation was observed, and significantly more chondrocyte death and cartilage erosion than in arthritic C57BL/6 mice. The synovial lining and peritoneal macrophages of na?ve DBA/1 mice expressed a significantly higher level of Fc gamma Rs than was seen in C57BL/6 mice. Moreover, elevated and prolonged expression of IL-1 was found after stimulation of these cells with immune complexes. Zymosan or streptococcal cell walls caused comparable inflammation and only mild cartilage destruction in all strains. We conclude that Fc gamma R expression on synovial macrophages may be related to the severity of synovial inflammation and cartilage destruction during ICA.     

Signal transduction mechanisms through Fc gamma receptors on the mouse macrophage surface.

Mouse macrophages and macrophage cell lines such as P388D1 or J774 carry at least two distinct Fc gamma receptors (Fc gamma R): one specific for the Fc portion of IgG2a (Fc gamma aR, also classified as Fc gamma RI) and another for IgG2b (Fc gamma 2bR, also classified as Fc gamma RII beta). These Fc gamma Rs should transmit, upon binding of an appropriate ligand, a specific signal that leads to the regulation of macrophage functions, as the interaction of immune complex with cell surface receptor has been shown to lead to suppression of the humoral immune response or B cell differentiation, to the destruction of target cells by antibody-dependent cell-mediated cytotoxicity, to activation of arachidonic acid metabolic cascade, to the phagocytosis of opsonized particles, or to the generation of superoxide anion. In this review, we first describe evidence that Fc gamma 2aR and Fc gamma 2bR are associated with casein kinase II and phospholipase A2 activity, respectively. We will then discuss a potential role for these enzymatic activities in signal transduction pathways that leads to the activation of the arachidonic acid metabolic cascade and adenylate cyclase, to the regulation of phagocytosis, and to the suppression of interferon-gamma action to induce Ia antigens.     

Effect of rat alveolar lining material on macrophage receptors

Resident alveolar macrophages of many rat strains lack detectable C receptors and cannot carry out C-mediated bacterial attachment and phagocytosis. It has not been established whether this lack of functional receptors is innate or is acquired by contact with the alveolar microenvironment. In the present studies, peritoneal macrophages treated with lavage under conditions designed to maintain viability and adherence to glass showed loss of detectability of C and Fc receptors. Depending on the concentration of lavage and the time allowed for recovery, this effect appeared to be reversible. Continued incubation of peritoneal macrophages with lavage fluid led to loss of adherence to glass and cell death. Lavage-treated 51Cr-labeled macrophages rapidly released radiolabel. Although transmission electron micrographs of lavage-treated peritoneal macrophages appeared normal, micrographs prepared with freeze-fracture techniques revealed clumping and asymmetric distribution of the intramembrane particles. Similar membrane abnormalities were present in untreated resident alveolar macrophages. The anti-receptor effect of rat lavage was not species-specific and lung lavage fluid from dogs, rabbits, and mice affected receptor detectability on rat macrophages. The anti-receptor factor in rat lavage was localized to the surfactant-containing fraction and was stable on heating at 60 degrees C. It was resistant to trypsin and partitioned into chloroform in the Bligh-Dyer extraction procedure, suggesting that it was a lipid. Purified diacyl phospholipids had no effect on macrophage receptors, but purified lysophospholipids mimicked many of the effects of surfactant. We conclude that lipids in the alveolar lining material affect alveolar macrophage membranes and receptor function.     

Activation of alveolar macrophages after lower respiratory tract infection.

Alveolar macrophage function has been studied in relation to bacterial infection of the lower respiratory tract. First, LRT macrophages were examined after exposure of rabbits to Listeria monocytogenes aerosols. Macrophages obtained from the LRT of animals 10 to 48 days after infection were activated, as evidenced by greater adherence to culture dishes and increased ability to ingest and kill both the original infecting organism and unrelated organisms, when compared to normal alveolar macrophages. Next, the in vitro effects on normal alveolar macrophages of incubation supernatants of control and antigen-stimulated lymphocytes (LRT and lymph node) from animals infected with L. monocytogenes or Streptococcus pneumoniae were evaluated. As manifested by increased adherence and phagocytosis, and an enhanced nonspecific bactericidal activity, alveolar macrophages were activated by the antigen-stimulated supernatants. These stimulated lymphocyte supernatants contain lymphokines (MIF), but the exact nature of the alveolar macrophage activating factor(s) remains to be determined. These observations, together with recent evidence that alveolar macrophages respond to lymphokines (MIF), suggest that the effector mechanism for cell-mediated immunity in the LRT is intact.     

Functional association of CD9 with the Fc gamma receptors in macrophages

CD9, a member of the tetraspan family of proteins, is highly expressed on macrophages. Although a clear function for the molecule has yet to be described, we have found that the anti-CD9 mAb activates mouse macrophages. The rat anti-CD9 mAb, KMC8.8, but not the F(ab')(2), induced tyrosine phosphorylation of proteins including syk and cbl and induced cell aggregation in the mouse macrophage cell line, J774, suggesting that co-cross-linking of CD9 and Fc gamma R was required for the signal. Co-cross-linking of CD9-Fc gamma R with KMC8.8 on macrophages from three different FcR-deficient mice, FcR gamma-chain(-/-), Fc gamma RIIB(-/-), and Fc gamma RIII(-/-), revealed that Fc gamma RIII is specific and crucial for syk phosphorylation. Although both KMC8.8 and the anti-Fc gamma RIIB/III mAb, 2.4G2, evoked similar phosphorylation patterns, only KMC8.8 induced cell aggregation. Additionally, KMC8.8 treatment led to reduce levels of TNF-alpha production and p42/44 extracellular signal-related kinase phosphorylation relative to 2.4G2 stimulation. Immunofluorescence staining showed that co-cross-linking of CD9-Fc gamma R with KMC8.8 induced filopodium extension before cell aggregation, which was followed by simultaneous colocalization of CD9, Fc gamma RIIB/III, Mac-1, ICAM-1, and F-actin at the cell-cell adhesion site. Moreover, KMC8.8 treatment of Fc gamma R-deficient macrophages revealed that the colocalization of CD9, Fc gamma RIII, Mac-1, and F-actin requires co-cross-linking of CD9-Fc gamma RIII, whereas co-cross-linking of CD9-Fc gamma RIIB induced the colocalization of only CD9 and Fc gamma RIIB. Our results demonstrate that co-cross-linking of CD9 and Fc gamma Rs activates macrophages; therefore, CD9 may collaborate with FcRs functioning in infection and inflammation on macrophages.     

IL-6 is a differentiation factor for M1 and WEHI-3B myeloid leukemic cells

IL-6 has multiple biologic activities in different cell systems including both the ability to support cell proliferation and to induce differentiation. We reported previously the isolation and functional expression of a mouse IL-6 (mIL-6) cDNA clone derived from bone marrow stromal cells. In this paper, we show that mIL-6 is a potent inducer of terminal macrophage differentiation for a mouse myeloid leukemic cell line, M1. Addition of mIL-6 to cultures of M1 cells rapidly inhibits their proliferation and induces phagocytic activity and morphologic changes characteristic of mature macrophages. These phenotypic changes are accompanied at the molecular level by a decrease in proto-oncogene c-myc mRNA accumulation and increases in Fc gamma R, proto-oncogenes c-fos and c-fms (CSF-1R) mRNA expression. Furthermore, IL-6 enhances the expression of Fc gamma R and c-fms in differentiation-responsive D+, but not unresponsive D- sublines of mouse myelomonocytic leukemic WEHI-3B cells. Together with our previous observation that IL-6 stimulates colony formation by normal myeloid progenitors, these results strongly suggest an important regulatory role for IL-6 in myeloid cell growth and differentiation.     

Z39Ig is co-expressed with activated macrophage genes

Z39Ig is a recently-identified gene with immunoglobulin-like domains whose function is unknown. We examined expression of Z39Ig in 1432 human cDNA libraries, and found it primarily in synovium of patients with rheumatoid arthritis, in placenta, and in lung. We analyzed its co-expression pattern using the Guilt-by-Association (GBA) algorithm, and found that it is most similar in expression to early genes in the classical complement system (C1qA, C1qB, C1qC, C1r, and C1 inhibitor), MHC class II genes (HLA-DR alpha, HLA-DR beta 1, and HLA-DP alpha 1), Fc receptors (Fc gamma RIIa and Fc epsilon R1), lysosomal protein (LAPTm5), tissue transglutaminase, and macrophage receptors (MARCO and CD163/M130). The sequence and expression data suggest that Z39Ig is a cell surface receptor, expressed in activated macrophages, and linked with the classical complement system, most likely in phagocytosis preceding antigen presentation. Knowledge of this gene may contribute to better understanding of the role of complement and activated macrophages in rheumatoid arthritis and systemic lupus.