Biomedical subjects

J van Damme

Publications and source records attributed to J van Damme.

At least 37 records · Page 2Linked to original sources

PubMed1994

Leukocyte recruitment by monocyte chemotactic proteins (MCPs) secreted by human phagocytes.

Phagocyte recruitment is an important immunological phenomenon in inflammation and cancer. A large family of selective chemotactic cytokines, designated chemokines, has recently emerged. Interleukin-8 (IL-8) is the prototype of such neutrophil activating factors, whereas MCP-1 is a well studied monocyte chemotactic protein. In vitro chemotactic assays were used to isolate and identify natural chemokines from mononuclear phagocytes and tumor cells. Additional new chemotactic proteins (MCP-2, MCP-3) attracting monocytes were also discovered by these methods. All chemokines are structurally related and show affinity for heparin. MCP-1, -2 and -3 have a comparable specific activity in monocyte chemotaxis assays. Specific and sensitive radioimmunoassays for MCP-1 and IL-8 were developed to study the regulation of their secretion by leukocytes. Monocytes or monocyte tumor cells produce MCP-1 and/or IL-8 in response to cytokines, virus, double stranded RNA, bacterial endotoxin, mitogen or phorbol ester. Granulocytes were found to secrete only minor amounts of MCP-1 and IL-8.

Amino Acid Sequence↗

PubMed1994

Receptors and transduction pathways for monocyte chemotactic protein-2 and monocyte chemotactic protein-3. Similarities and differences with MCP-1.

MCP-2 and MCP-3 are recently identified members of the Cys-Cys chemokine family with high sequence similarity with MCP-1 (62% and 71%, respectively). The present study was aimed at defining receptor usage and signal transduction pathways of MCP-2 and MCP-3 in human monocytes in comparison with MCP-1. MCP-2 and MCP-3 induced migration of monocytes with a typical bell-shaped curve and maximal response at 10 and 50 ng/ml, respectively. The maximal response elicited by MCP-2 and MCP-3 was lower (approximately 60%) than that of MCP-1. Pertussis toxin (PTox) inhibited the chemotactic activity of MCP-3 and MCP-1 (IC50 = 6.2 and 4.4 ng/ml, respectively), whereas cholera toxin (CTox) had little effect on these two chemokines (IC50 > 1000 ng/ml). In contrast, MCP-2-induced chemotaxis was blocked by CTox (IC50 = 75 ng/ml) and relatively unaffected by PTox. MCP-3 and MCP-1 induced a rapid increase in intracellular Ca2+ concentration, whereas MCP-2, in the range of concentrations active on chemotaxis, did not. MCP-1-, MCP-2-, and MCP-3-induced chemotactic responses were blocked by C-I, a serine/threonine kinase inhibitor, and by genistein, a tyrosine kinase inhibitor, with the MCP-2 response being more sensitive than those induced by MCP-1 and MCP-3. MCP-1 and MCP-3 rapidly induced arachidonic acid release whereas MCP-2 was ineffective. MCP-1 and MCP-3 cross-desensitized with each other in terms of Ca2+ transients and displaced with a comparable efficiency labeled MCP-1 from human monocytes. On the other hand, MCP-2 did not cross-desensitize with MCP-1 and MCP-3 and only partially (20%) displaced labeled MCP-1. Thus, in spite of high sequence similarity, MCP-2 differed considerably from MCP-1 and MCP-3 in terms of sensitivity to CTox and PTox, arachidonate and calcium mobilization, and capacity to compete for labeled MCP-1.

Arachidonic Acid↗

PubMed1994

Essential role for natural killer cells in the lethal lipopolysaccharide-induced Shwartzman-like reaction in mice.

Observations in our laboratory have provided evidence that interferon-gamma (IFN-gamma) is a key regulator of inflammatory responses to bacterial lipopolysaccharide (LPS) (Heremans et al., J. Exp. Med. 1990. 171: 1853): treatment of mice with neutralizing monoclonal antibody against IFN-gamma was found to completely prevent lethal shock reactions, in particular the generalized Shwartzman reaction, whereas treatment with IFN-gamma sensitized the mice to the development of such reactions. Since activated T cells and natural killer (NK) cells are the main if not the only potential source of LPS-induced IFN-gamma, we investigated the relative importance of these cells in the development of the generalized Shwartzman-like reaction in mice by depleting them selectively with relevant monoclonal antibodies. Treatment with antibodies directed against the CD4+ T cells subset was not effective in protecting mice. Anti-CD8 antibody did attenuate the reaction to some extent. However, markedly reduced mortality was seen in mice which were depleted of NK cells by systemic administration of polyclonal anti-asialo GM1 or monoclonal anti-NK1.1 antibodies. Failure of T cells to promote the Shwartzman reaction was also evidenced by the observation that thymus-less nude mice, which are deficient in T cells, were more rather than less sensitive to the reaction. Approximately 20 times less LPS was needed to induce the lethal reaction in these mice than in NMRI mice and 58 times more anti-IFN-gamma antibody was required to block mortality. Nu/nu mice reportedly have an over-active NK cell compartiment. IFN-gamma production by these cells in LPS-treated mice may account for the augmented sensitivity. Our data suggest that NK cells may be the most important source of endogenous IFN-gamma which mediates the LPS-induced lethal reactions in mice.

Animals↗

PubMed1994

Induction of natural killer cell migration by monocyte chemotactic protein-1, -2 and -3.

Under certain physiological and pathological conditions, natural killer (NK) cells rapidly accumulate in tissues. Chemokines are an essential component of the current paradigm of leukocyte recruitment. The present study was designed to investigate the responsiveness of NK cells to the prototypic C-C chemokine, monocyte chemotactic protein-1 (MCP-1). MCP-1 induced migration across filters of interleukin (IL)-2-activated NK cells, whereas it was a weak attractant for unstimulated cells. Maximal induction of migration required a positive concentration gradient between the lower and the upper compartment of the chemotaxis chamber. Preliminary characterization of the MCP-1 receptor on NK cells indicated that the chemotactic response to MCP-1 was blocked by pre-treatment of cells with Bordetella pertussis toxin, and MCP-1 but not IL-8 displaced 125I-labeled MCP-1 from IL-2-activated NK cells. The related chemokines MCP-2 and MCP-3 were also active--though less potent--attractants for activated NK cells. Thus the spectrum of action of MCP-1, -2 and -3 encompasses NK cells and chemokines are likely to play a role in regulating extravasation of these cells.

Binding, Competitive↗

PubMed1993

NAD-binding site of the C3-like ADP-ribosyltransferase from Clostridium limosum.

Treatment of the Rho-ADP-ribosylating C3-like transferase from Clostridium limosum by ultraviolet irradiation in the presence of [carbonyl-14C]NAD incorporated 1 mol of label/mol of exoenzyme. Concomitantly, the transferase and NAD glycohydrolase activity was impaired. A peptide containing the radiolabel was obtained by proteolysis with either staphylococcal protease V8 or trypsin. Their amino acid sequences were Ala/Asp-Gly-Tyr-Ile-Glu-Pro-Ile-Ser-Thr-Phe-Lys-Gly-Gln-Leu-X-Val-Leu-Le u-Pro- Arg and Gly-Gln-Leu-X-Val-Leu-Leu-Pro-Arg, respectively. These sequences correspond with regions Ala-160 through Arg-179 and Gly-171 through Arg-179, respectively, of the very similar Clostridium botulinum C3 transferase, with X being Glu in the unlabeled enzyme. This identifies the glutamic acid residue that corresponds to Glu-174 of C. botulinum C3 transferase as part of the NAD-binding site of the catalytic center of the C. limosum exoenzyme.

ADP Ribose Transferases↗

PubMed1993

Differential regulation of gelatinase B and tissue-type plasminogen activator expression in human Bowes melanoma cells.

A comparison of the production of tissue-type plasminogen activator (t-PA) and gelatinases A and B was made at the mRNA and protein levels in human Bowes melanoma cells treated with phorbol myristate acetate (PMA). Immunocytochemical analysis confirmed previous quantitative data on PMA-mediated induction of t-PA. It also showed that t-PA immunoreactivity can be restrained to the local environment of the producing cell, most probably by interaction with extracellular matrix components. Zymographical analysis showed that gelatinase B protein was induced by PMA, whereas gelatinase A remained at the constitutive level. Protein kinase C (PKC) appeared to be involved in this regulation since, after PMA treatment (1) the PKC activity was found to be translocated from the cytosol to the particulate fraction of the cells and (2) addition of staurosporine and H-7 blocked the gelatinase B increase. Northern-blot hybridization showed a transient rise in t-PA and gelatinase B mRNA levels whereas gelatinase A mRNA levels remained unchanged. When c-fos and c-jun mRNAs were investigated, only that of c-fos was affected by PMA. Activation by PMA can be kinetically ordered as follows: translocation of PKC to the membrane fraction, transcription of the c-fos gene and eclipsing of gelatinase B mRNA, increase in steady-state mRNA levels of t-PA and gelatinase B and, finally, secretion of t-PA and gelatinase B glycoproteins. Our data also suggest that various proteases that are known to cooperate in the remodeling of the extracellular matrix can be differently regulated in one tumor-cell type.

Cell Compartmentation↗

PubMed1993

Increased circulating interleukin-6 (IL-6) activity in endotoxin-challenged mice pretreated with anti-IL-6 antibody is due to IL-6 accumulated in antigen-antibody complexes.

Mice pretreated with monoclonal anti-interleukin-6 (IL-6) antibody and then challenged with lipopolysaccharide (LPS), paradoxically develop higher levels of circulating biological IL-6 activity, as measured by the hybridoma growth promotion assay, than mice similarly challenged but not pretreated with antibody. Here we provide evidence that this increased biological activity was entirely accounted for by the presence of increased amounts of IL-6 protein, which could be isolated by immunoaffinity chromatography and subsequently visualized after gel electrophoresis. Chromatography on a protein G matrix and a sandwich ELISA allowed to demonstrate that all IL-6 present in the serum was in the form of antigen-antibody complexes. Serum samples of antibody-treated animals which contained the highest biological activity typically contained near equimolar concentrations of IL-6 and antibody. In vitro neutralization tests with pure antibody and IL-6 demonstrated that, with both antibodies tested, more than 1000-fold molar excess of antibody is needed for neutralization in the hybridoma growth assay. It is concluded that increased biological activity in serum of the anti-IL-6 antibody-treated mice is due to sequestration of the endogenous IL-6 in the form of antigen-antibody complexes which, due to the lack of sufficient antibody excess, produce nearly full activity in the hybridoma growth assay.

Animals↗

PubMed1993

Continuous infusion of interleukin-6 in sublethally irradiated mice accelerates platelet reconstitution and the recovery of myeloid but not of megakaryocytic progenitor cells in bone marrow.

Interleukin-6 (IL-6) is a pleiotropic cytokine that enhances the maturation of megakaryocytes. In mice, in vivo treatment with IL-6 results in elevated platelet counts both in untreated animals and after myelosuppressive therapy. In this study, we assessed the effect of continuous infusion of IL-6 in sublethally irradiated (7 Gy) mice on peripheral blood cell counts and progenitor cells in bone marrow and spleen. Female Swiss mice were treated by continuous infusion with 1 or 10 micrograms IL-6 per day for 7 or 14 days. Continuous infusion of IL-6 for 7 days resulted in elevated levels of circulating IL-6 (mean: 1872 pg/mL vs. 100 pg/mL for phosphate-buffered saline [PBS]-treated controls) and in an accelerated reconstitution of platelets starting at day 12 after irradiation. In IL-6-treated animals, the 50% pretreatment platelet count was reached on day 15 vs. day 21 for irradiated controls receiving no IL-6. Treatment with IL-6 for 14 days resulted in a further increase in platelet counts, exceeding the pretreatment counts. The number of colony-forming units-megakaryocyte (CFU-Mk) was significantly elevated from day 6 to 18 in the spleen but not in bone marrow. To assess the contribution of extramedullary megakaryocytopoiesis in the spleen to IL-6-induced platelet recovery, IL-6 was also administered to splenectomized mice. The stimulatory effect of IL-6 on platelet recovery was preserved in these animals, indicating that megakaryocytopoiesis in the spleen did not contribute to the accelerated recovery of platelets. The neutrophil counts were elevated during IL-6 treatment and became similar to controls after cessation of therapy, whereas the numbers of colony-forming units-granulocyte/macrophage (CFU-GM) in the bone marrow were elevated from day 9 to 24 in all animals treated with 10 micrograms IL-6 per day. In conclusion, continuous infusion of IL-6 stimulates platelet recovery after irradiation without increasing the number of CFU-Mk and conversely stimulates the proliferation of myeloid progenitor cells without an effect on neutrophil reconstitution.

Animals↗

PubMed1992

Evidence for new phosphorylation sites for protein kinase C and cyclic AMP-dependent protein kinase in bovine heart 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.

Bovine heart 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) was phosphorylated by incubation with [gamma-32P]MgATP and cyclic AMP-dependent protein kinase (PKA) or protein kinase C (PKC). After digestion with chymotrypsin, the phosphorylation sites for the two protein kinases were identified by peptide mapping, and microsequencing. Evidence for new phosphorylation sites for PKA (Ser-483) and PKC (Ser-84 and Ser-466) was obtained.

Amino Acid Sequence↗

PubMed1992

Purification and characterization of an ADP-ribosyltransferase produced by Clostridium limosum.

We purified a novel ADP-ribosyltransferase produced by a Clostridium limosum strain isolated from a lung abscess and compared the exoenzyme with Clostridium botulinum ADP-ribosyltransferase C3. The C. limosum exoenzyme has a molecular weight of about 25,000 and a pI of 10.3. The specific activity of the ADP-ribosyltransferase is 3.1 nmol/mg/min with a Km for NAD of 0.3 microM. Partial amino acid sequence analysis of the tryptic peptides revealed about 70% homology with C3. The novel exoenzyme modifies selectively the small GTP-binding proteins of the rho family in human platelet membranes presumably at the same amino acid (asparagine 41) as known for C3. Recombinant rhoA and rhoB serve as substrates for C3 and the C. limosum exoenzyme. Whereas recombinant rac1 protein is only marginally ADP-ribosylated by C3 or by the C. limosum exoenzyme in the absence of detergent, in the presence of 0.01% sodium dodecyl sulfate rac1 is modified by C3 but not by the C. limosum exoenzyme. Recombinant CDC42Hs protein is a poor substrate for C. limosum exoenzyme and is even less modified by C3. The C. limosum exoenzyme is auto-ADP-ribosylated in the presence of 0.01% sodium dodecyl sulfate by forming an ADP-ribose protein bond highly stable toward hydroxylamine. The data indicate that ADP-ribosylation of small GTP-binding proteins of the rho family is not unique to C. botulinum C3 ADP-ribosyltransferase but is also catalyzed by a C3-related exoenzyme from C. limosum.

ADP Ribose Transferases↗

PubMed1992

Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes.

Microsequencing of proteins recovered from two-dimensional (2-D) gels is being used systematically to identify proteins in the master human keratinocyte 2-D gel database. To date, about 250 protein spots recorded in human 2-D gel databases have been microsequenced and, of these, 145 are recorded in the keratinocyte database under the entry partial amino acid sequence. Coomassie Brilliant Blue-stained protein spots cut from several (up to 40) dry gels were concentrated by elution-concentration gel electrophoresis, electroblotted onto PVDF membranes and digested in situ with trypsin. Eluting peptides were separated by reversed-phase HPLC, collected individually and sequenced. Computer search using the FASTA and TFASTA programs from Genetics Computer Group indicated that 110 of the microsequenced polypeptides shared significant similarity with proteins contained in the PIR, Mipsx or GenEMBL databases. Only 35 polypeptides corresponded to hitherto unknown proteins. Peptide sequences of all 145 proteins are listed together with their coordinates (apparent molecular weight and pI) in the keratinocyte database.

Amino Acid Sequence↗

PubMed1991

Natural human monocyte gelatinase and its inhibitor.

Gelatinases produced by stimulated peripheral blood monocytes were detected by substrate zymography and were compared with those derived from tumor cells. Stimulated monocytes were found to produce an 85 kDa gelatinase which co-migrated upon electrophoretic separation and cross-reacted in immunoprecipitation experiments with a phorbol ester inducible metalloprotease from human tumor cells. The intact natural gelatinase (85 kDa), a high molecular weight and complexed gelatinase as well as a proteolytic fragment (25 kDa) were purified by substrate- and antibody-affinity chromatography techniques. Aminoterminal sequence analysis showed that natural monocyte gelatinase occurs as a truncated form of tumor cell gelatinase/type IV collagenase. Furthermore, peripheral blood monocytes were found to also produce a tissue inhibitor of metalloproteases (TIMP). TIMP was co-purified with gelatinase on gelatin sepharose and identified by microsequencing. The balanced and regulated production of gelatinase and TIMP might be important in monocyte migration and tissue remodeling.

Cells, Cultured↗

PubMed1990

Purification, cDNA-cloning and expression of human diacylglycerol kinase.

Diacylglycerol (DG) kinase attenuates the level of the second messenger DG in signal transduction, and therefore possibly modulates protein kinase C (PKC). DG kinase was purified to homogeneity from human white blood cells, showing an Mr of 86 kDa as determined by SDS-PAGE and gel filtration. Two amino acid sequences of tryptic peptides from DG kinase were determined and degenerate oligonucleotides were prepared and used in the polymerase chain reaction. An amplified DNA fragment was subsequently used to clone the full-length human DG kinase cDNA. This sequence is the human homolog of a porcine DG kinase cDNA sequence reported recently. The sequence contains a double EF-hand structure typical for Ca2+ binding proteins. DG kinase further contains a double cysteine repeat that is present in all PKC isoforms, where it constitutes the phorbol ester (and most likely diacylglycerol) binding site. Therefore we speculate that the double cysteine repeat in DG kinase is involved in DG binding. DG kinase is transcribed as a single mRNA of 3.2 kb, that is highly expressed in T-lymphocytes. The human DG kinase cDNA when transfected in mammalian cells (COS-7) results in a 6-7-fold increase of DG kinase activity.

Adenosine Triphosphate↗

PubMed1990

Two-dimensional gel electrophoresis, protein electroblotting and microsequencing: a direct link between proteins and genes.

We have used two-dimensional gel electrophoresis as a general "preparative" method to purify proteins for microsequencing analysis. In the first experiments, proteins derived from a total extract of Nicotiana tabacum leaf tissue were directly blotted from the gel onto poly(4-vinyl-N-methylpyridinium iodide)-coated glass fiber sheets. The major spots were excised and subjected to NH2-terminal sequence analysis, which made it possible to identify five of the eight selected proteins, while two more were recognized by generated internal sequences. In a second set of experiments, proteins of human origin were separated on multiple two-dimensional gels and the Coomassie Brilliant Blue-stained spots were excised from the gels. The combined spots were re-eluted and concentrated in a new gel and blotted on Immobilon. They were fragmented by in situ proteolysis and the generated peptides were separated by reverse phase-high performance liquid chromatography and sequenced. At the average, the internal sequences that were obtained covered 35 residues per protein and allowed unambiguous identification of 13 of the 23 proteins analyzed so far. The sequence information obtained of the unidentified proteins is sufficient for further cloning. These results demonstrate that systematic sequence analysis of the major proteins seen in two-dimensional gels is within the reach of current technologies. This offers a unique opportunity to link information contained in protein databases with known or forthcoming DNA sequence data.

Amino Acid Sequence↗

PubMed1990

Purification and N-terminal sequencing of style glycoproteins associated with self-incompatibility in Petunia hybrida.

We report isolation and N-terminal amino acid sequencing of three style glycoproteins, which segregate with three S (self-incompatibility) alleles of Petunia hybrida. The S-glycoproteins were expressed mainly in the upper part of the pistil and showed an increasing concentration during flower development. The glycoproteins were purified by a combination of ConA-Sepharose and cation exchange fast protein liquid chromatography. The amount of S-glycoproteins recovered from style extracts varied from 0.5 to 1.6 micrograms per style, which was 40-60% of the amount recovered by a simplified analytical method. N-terminal amino acid sequences of S1-, S2- and S3-glycoprotein showed homology within the fifteen amino terminal residues. These amino acid sequences were compared with the previously published sequences of S-glycoproteins from Nicotiana alata and Lycopersicon peruvianum.

Alleles↗

PubMed1990

Interleukin-1 and interleukin-6 in psoriasis.

We report on the levels of expression of IL-1 and IL-6 in skin from psoriasis patients. Different approaches were pursued. Initially, the levels of IL-1 beta and IL-6 were measured in suction blister fluid from lesional and uninvolved skin from psoriasis patients, using a sensitive enzyme-linked immunoabsorbent assay (ELISA) and bio-assay. Skin sections were also examined for the presence of IL-1 and IL-6 using IL-1 beta- and IL-6-specific antibodies. Finally, the expression of IL-1 and IL-6 mRNA was determined in cultured keratinocytes (KC) and fibroblasts from psoriasis skin. Suction blister fluid from lesional and uninvolved psoriasis skin and from skin of healthy individuals did not contain detectable levels (greater than 100 pg/ml) of IL-1 beta. Blister fluid from psoriasis lesions contained low but significant levels of IL-6, whereas the serum levels of IL-6 in these patients was undetectable. Using cryostat skin sections and an IL-1 beta-specific monoclonal antibody (MoAb) in an indirect immunoperoxidase technique, a diffuse staining in the entire epidermis was observed in sections of uninvolved skin from psoriasis patients. In cryostat sections of psoriasis lesions, a faint diffuse staining of the epidermis and a pronounced "dot-like" intracellular staining pattern was observed. On the other hand, the same IL-1 beta-specific MoAb showed, in a indirect immunofluorescence technique using unfixed epidermal cells, bright membrane staining in epidermal cell suspensions from psoriasis lesions. Slightly elevated levels of IL-1 beta and IL-1 alpha mRNA were observed in cultured KC from psoriasis lesions as compared to those in normal KC and in the HEp-2 cell line. Very low levels of IL-6 mRNA were expressed in KC from psoriasis lesions and healthy individuals. Fibroblasts from psoriasis lesions expressed extremely low levels of IL-1 alpha and IL-1 beta, but high levels of IL-6 mRNA. The results point to a paradoxical situation in psoriatic skin: blister fluid from psoriasis lesions contains no IL-1 beta, whereas IL-1 beta is overexpressed on the plasma membrane and in the intracellular compartment of epidermal cells. This finding may help in explaining the observed absence of IL-1 in aqueous extracts of psoriatic scales. Because cultured KC from psoriasis lesions express minimal levels of IL-6 mRNA. dermal fibroblasts, probably together with the inflammatory infiltrate, may represent a major source of IL-6 in psoriasis lesions in vivo.

Blister↗

PubMed1989

Human granulocyte chemotactic peptide (IL-8) as a specific neutrophil degranulator: comparison with other monokines.

The influence of human monocyte-derived chemotactic peptide (GCP/IL-8) on degranulation of neutrophils was investigated in relation to that of other monokines. GCP/IL-8 promoted a dose-dependent release of lactoferrin from specific granules but had no effect on enzyme release from primary granules. From the other monokines that were tested, tumour necrosis factor alpha (TNF alpha) also induced degranulation, while IL-1 beta and IL-6 scored negatively. TNF alpha-induced lactoferrin release was enhanced by cytochalasin B pretreatment of the granulocytes, while GCP/IL-8-promoted degranulation was not. In contrast to GCP, TNF alpha also caused the release of LDH, suggesting a non-specific cell destruction. These observations further support the view that, unlike the other monokines, GCP/IL-8 is a true and specific granulocyte activator.

Biological Factors↗

PubMed1988

Interleukin 1 induces human marrow stromal cells in long-term culture to produce granulocyte colony-stimulating factor and macrophage colony-stimulating factor.

Pure interleukin 1 (IL 1) was found to stimulate established human bone marrow stromal layers in long-term culture to produce colony-stimulating activity (CSA). Maximal concentrations in the culture medium were reached 24 hours after a single IL 1 pulse. The effect could be neutralized by a specific rabbit anti-IL 1 antiserum. Stromal layers, once stimulated by IL 1, continued to release CSA into the culture medium in the absence of exogenous IL 1. A second IL 1 pulse induced CSA release in an identical manner, as did the primary stimulation, indicating that the CSA released was actively produced. Using specific immunologic assays, both granulocyte colony-stimulating factor (G-CSF) and macrophage CSF (M-CSF) could be identified in the culture supernatants, and production of both factors was inducible by IL 1. Shortly after initiation of the long-term marrow cultures "spontaneous" G-CSF and M-CSF release occurred. The release of G-CSF diminished following addition of the anti-IL 1 antiserum, indicating that endogenous production of IL 1 by stromal cells had contributed to this effect. These results further support the role of IL 1 as an important modulator of CSF production by cells of the hematopoietic microenvironment.

Bone Marrow↗