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Biomedical subjects

M M Faas

Publications and source records attributed to M M Faas.

At least 19 recordsLinked to original sources
PubMed2002

Monocyte intracellular cytokine production during human endotoxaemia with or without a second in vitro LPS challenge: effect of RWJ-67657, a p38 MAP-kinase inhibitor, on LPS-hyporesponsiveness.

In the present study, we investigated the effect of RWJ-67657, a p38 MAP kinase inhibitor, upon in vivo LPS-induced monocyte cytokine production and upon monocyte LPS-hyporesponsiveness. Thirty minutes before a single injection of LPS (4 ng/kg BW), healthy male volunteers received a single oral dose of RWJ-67657 at increasing dosages (0-1400 mg). Blood samples (pre-medication, 3, 6 and 24 h after LPS) were immediately incubated with LPS (reflecting LPS-hyporesponsiveness) or without LPS (reflecting in vivo monocyte stimulation) for 4 h at 37 degrees C. Following red blood cells lysis and white blood cell permeabilization, cells were labelled with alpha-CD14-FITC and alpha-IL-1beta, alpha-IL-12 or alpha-TNFalpha (PE-labelled), fixed, and analysed using flow cytometry. In vivo LPS injection resulted in an increased percentage of circulating monocytes producing IL-1beta, TNFalpha and IL-12 only at 3 h after the LPS injection. This was dose-dependently inhibited by RWJ-67657 treatment. LPS-hyporesponsiveness to in vitro LPS treatment was most prominent at 3 and 6 h after the in vivo LPS injection; compared with pre-medication monocytes, at these intervals a reduced percentage of monocytes produced IL-1beta, TNFalpha or IL-12 after the in vitro LPS stimulus. At t = 6 h, this LPS-hyporesponsiveness could dose-dependently be inhibited by RWJ-67657 treatment of the volunteers. We therefore conclude that p38 MAP kinase inhibition with RWJ-67657 inhibited monocyte production of cytokines following in vivo LPS injection. Treatment with RWJ-67657 also reversed the LPS-hyporesponsiveness. Whether this result can be extended to the clinical situation remains to be elucidated. Patients with sepsis or an otherwise high risk for multi-organ failure are potential study groups.

Endotoxemia↗
PubMed2001

The immune response during the luteal phase of the ovarian cycle: increasing sensitivity of human monocytes to endotoxin.

OBJECTIVE: To test the hypothesis that during the luteal phase of the human ovarian cycle, as compared with the follicular phase, the percentage of cytokines producing peripheral monocytes after in vitro stimulation with endotoxin is increased. DESIGN: Prospective study. SETTING: Academic research institution. PATIENT(S): Women with regular menstrual cycles. INTERVENTION(S): Blood samples were collected between days 6 and 9 of the menstrual cycle (follicular phase) and between days 6 and 9 of the menstrual cycle following the LH surge (luteal phase). MAIN OUTCOME MEASURE(S): Percentages of tumor necrosis factor (TNF)-alpha-, interleukin (IL)-1 beta-, and IL-12-producing monocytes as well as total white blood cell (WBC) count, differential WBC counts, and plasma 17 beta-estradiol and progesterone concentrations. RESULT(S): Mean plasma 17 beta-estradiol and progesterone concentrations, percentage of TNF-alpha- and IL-1 beta-producing monocytes, WBC counts, and granulocyte cell count were significantly increased in the luteal phase as compared with the follicular phase of the ovarian cycle. The percentage of IL-12-producing monocytes, monocyte count and lymphocyte count did not vary between the 2 phases of the ovarian cycle. CONCLUSION(S): Together with an increase in progesterone and 17 beta-estradiol during the luteal phase, there is an increase in percentage TNF-alpha- and IL-1 beta-producing peripheral monocytes after in vitro stimulation with endotoxin as compared with the follicular phase of the ovarian cycle. Whether this increased sensitivity of monocytes for proinflammatory stimuli during the luteal phase is due to increased plasma levels of progesterone or 17 beta-estradiol needs further investigation.

Adult↗
PubMed2001

Cytokine production by natural killer lymphocytes in follicular and luteal phase of the ovarian cycle in humans.

PROBLEM: The aim of this study was to test the hypothesis that, during luteal phase of the ovarian cycle, as compared with follicular phase, the cytokine productive capacity of peripheral natural killer (NK)-lymphocytes in humans is shifted towards a "Th2-type"-like response. METHOD OF STUDY: Intracellular Th1 and Th2 cytokine production by in vitro activated peripheral NK-lymphocytes in a whole blood preparation of the follicular and the luteal phase of the ovarian cycle was measured by flow cytometry. RESULTS: There was no difference in interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10 cytokine production in activated NK-lymphocytes when comparing luteal phase with follicular phase of the ovarian cycle. However, there was a significant increase in peripheral NK-lymphocyte number in luteal phase compared with follicular phase. CONCLUSION: The cytokine productive capacity of peripheral NK-lymphocytes is not shifted towards a "Th2-type"-like response in the luteal phase as compared with the follicular phase of the ovarian cycle in humans.

Adult↗
PubMed2000

Activation of peripheral leukocytes in rat pregnancy and experimental preeclampsia.

OBJECTIVE: The aim of this study was to search for activation markers of peripheral leukocytes in experimental preeclampsia in the rat. STUDY DESIGN: Experimental preeclampsia was induced in 14-day-pregnant rats by infusion of endotoxin (1.0 microg/kg body weight). For comparison, rats with normal pregnancies that were infused with sodium chloride solution and cyclic rats that were infused with either endotoxin or sodium chloride solution were used. At various points before and after the infusion, blood samples were withdrawn and analyzed by means of whole-blood flow cytometry to evaluate expression of inflammation-associated adhesion molecules (CD11b, CD11a, CD49d, and CD62L) and CD14 on the leukocytes. RESULTS: Normal pregnancy was associated with increased CD11b (granulocytes and monocytes), CD11a (monocytes and lymphocytes), and CD49d (granulocytes, monocytes, and lymphocytes) expression. In addition to these changes found in normal pregnancy, reduced CD62L and increased CD11a and CD49d expression was found on granulocytes after endotoxin treatment of pregnant rats. No effect of endotoxin was observed in cyclic rats. CONCLUSION: Leukocytes of rats with experimental preeclampsia and, to a lesser extent, those of rats with normal pregnancies had an activated phenotype. These results are consistent with our previous findings in human subjects and suggest that (experimental) preeclampsia results from a generalized inflammatory response.

Animals↗
PubMed2000

Suppression by developing ovarian follicles of the low-dose endotoxin-induced glomerular inflammatory reaction in the pregnant rat.

OBJECTIVE: In the current study the role of developing ovarian follicles in the control of the endotoxin-induced pregnancy-specific inflammatory reaction was evaluated. STUDY DESIGN: Follicular development was induced in pregnant rats (n = 20) by means of daily intraperitoneal injections of follicle-stimulating hormone from day 11 of pregnancy until the end of the experiment. Control pregnant rats (n = 20) received daily sodium chloride injections. All pregnant rats were infused for 1 hour with either 2 mL endotoxin solution (1.0 microg/kg body weight) or 2 mL sodium chloride solution on day 14 and killed 4 hours or 3 days later. At death, the left kidneys were snap-frozen and immunohistologically stained for the presence of polymorphonuclear leukocytes and monocytes. RESULTS: The results show that in control pregnant rats endotoxin significantly increased glomerular polymorphonuclear leukocyte and monocyte numbers at both 4 hours and 3 days after endotoxin infusion. Induction of follicular development did not affect glomerular polymorphonuclear leukocyte number after endotoxin infusion but significantly decreased the number of monocytes in the glomeruli at both 4 hours and 3 days after endotoxin infusion. CONCLUSION: We conclude that follicles stimulated with follicle-stimulating hormone produce a follicular factor or factors that are able to prevent the endotoxin-induced influx of monocytes into the glomeruli of pregnant rats. It is suggested that these factors play a role in the control of inflammatory processes associated with reproduction, including the disease of pregnancy, preeclampsia.

Animals↗
PubMed2000

Corticosterone treatment of pregnant low dose endotoxin-treated rats: inhibition of the inflammatory response.

PROBLEM: Can the endotoxin-induced inflammatory response, underlying experimental pre-eclampsia, in pregnant rats be inhibited by corticosterone? METHOD OF STUDY: On day 10 of pregnancy, rats were implanted with pellets containing 25% corticosterone and 75% cholesterol (n = 10) or with 100% cholesterol-pellets (n = 10). On day 14 of pregnancy, rats were infused with either endotoxin (1.0 microg/kg bw) or saline. Three days later, they were sacrificed. Cryostat kidney sections were immunohistologically stained for the presence of neutrophils (PMN) and monocytes (MO) and the expression of inflammation-associated adhesion molecules. RESULTS: In cholesterol-treated rats, endotoxin significantly increased glomerular numbers of PMN and MO, glomerular expression of ICAM-1 and VCAM-1 and glomerular numbers of LFA-1 and VLA-4-positive cells as compared with saline. Corticosterone treatment significantly inhibited glomerular infiltration of PMN, MO and LFA-1 positive cells after endotoxin infusion. It did not affect glomerular ICAM-1 or VCAM-1 expression or numbers of VLA-4 positive cells. CONCLUSIONS: It is concluded that pre-treatment with corticosterone inhibits the low dose endotoxin-induced glomerular inflammatory reaction in pregnant rats, most likely by inhibiting LFA-1 expression, thereby decreasing the adhesiveness of inflammatory cells for activated endothelial cells.

Animals↗
PubMed1999

Pregnancy enhances the sensitivity of glomerular ecto-adenosine triphosphate-diphosphohydrolase to products of activated polymorphonuclear leukocytes.

To test the hypothesis that pregnancy enhances the sensitivity of glomerular ecto-adenosine triphosphate-diphosphohydrolase to products of activated polymorphonuclear leukocytes, cryostat-cut kidney sections of pregnant and cycling rats were exposed to activated polymorphonuclear leukocytes and subsequently stained for ecto-adenosine triphosphate-diphosphohydrolase activity. The results show that the levels of ecto-adenosine triphosphate-diphosphohydrolase activity of pregnant rats showed a significantly greater decrease after incubation with activated polymorphonuclear leukocytes than did those of cycling rats.

Adenosine Triphosphatases↗
PubMed1999

Pregnancy aggravates proteinuria in subclinical glomerulonephritis in the rat.

Because subclinical renal disease may be aggravated during pregnancy--as reflected in the occurrence of proteinuria, for example--we investigated whether a subclinical glomerulonephritis (SG) in the non-pregnant rat (passive Heymann nephritis), a condition without proteinuria, is aggravated when the animals become pregnant and, if so, whether this is associated with a glomerular inflammatory reaction. SG was induced in non-pregnant rats 8 days before pregnancy. On day -1, part of the group of rats became pregnant. Three experiments were performed. In experiment 1, 4-hour urine albumin excretions and blood pressure (tail cuff) were measured. In experiment 2, the glomerular filtration rate (GFR) was measured with the chromium 51-labeled ethylenediaminetetraacetic acid method, while in experiment 3, parameters characteristic of a glomerular inflammation were studied. Experiment 1 revealed that non-pregnant rats with SG did not exhibit proteinuria. However, after the rats became pregnant, a significant proteinuria occurred, without an increase in systolic blood pressure. Experiment 2 revealed that the GFR did not increase in pregnant rats with SG, while experiment 3 showed that only pregnant animals exhibited a significant glomerular inflammation; this glomerular inflammation was characterized by intraglomerular influx of polymorphonuclear cells and monocytes. The results suggest that an SG in the rat may flare up during pregnancy. This exacerbation is characterized by proteinuria and coincides with a glomerular inflammatory reaction. It is suggested that proteinuria and the glomerular inflammatory reaction are causally related and promoted by the pregnant condition.

Albuminuria↗
PubMed1999

Effect of estradiol and progesterone on the low-dose endotoxin-induced glomerular inflammatory response of the female rat.

PROBLEM: Is the endotoxin-induced glomerular inflammatory response of the female rat under ovarian control? METHOD OF STUDY: Ovariectomized rats (OVX), with or without progesterone (OVX-P) or estradiol (OVX-E) treatment, as well as rats in the follicular or luteal phase of the ovulatory cycle were infused with endotoxin or saline and sacrificed 3 days later. Cryostat kidney sections were immunohistologically stained for the presence of neutrophils and monocytes (MO) and the expression of adhesion molecules. RESULTS: After endotoxin, the glomerular number of neutrophils and the number of MAC-1 positive cells were increased in luteal-phase and in OVX-P rats, and the number of glomerular Mø was increased in luteal-phase, OVX, OVX-E, and OVX-P rats. Endotoxin increased ICAM-1 expression in all groups of rats, except in follicular-phase rats. The glomerular number of LFA-1- and VLA-4 positive cells following endotoxin were only increased in OVX rats. CONCLUSIONS: It is concluded that endotoxin-induced monocyte infiltration and ICAM-1 expression are inhibited by a factor produced during the follicular phase, probably by developing follicles. Infiltration of neutrophils and expression of MAC-1, LFA-1, VLA-4 seem to be under control of progesterone or estradiol.

Animals↗
PubMed1998

Superoxide-mediated glomerulopathy in the endotoxin-treated pregnant rat.

In the present study the role of superoxide in the glomerular damage in the low-dose endotoxin-infused pregnant rats was investigated. On day 14 of pregnancy, 12 rats were infused for 1 h with 1.0 microgram/kg bw endotoxin via a permanent jugular vein cannula. Of these rats, 6 were treated with SOD both prior to endotoxin infusion (7,000 U/kg) and 30 min (7,000 U/kg) and 4 h (14,000 U/kg) after the start of the infusion (SOD rats). The other 6 rats received no SOD treatment (endotoxin rats). Control pregnant rats were infused for 1 h with saline (saline rats; n = 6). Urinary albumin was measured on days 15 and 19 of pregnancy. On day 21, rats were sacrificed and kidney specimens were snap-frozen. Cryostat kidney sections were stained for fibrinogen, ecto-ATP diphosphohydrolase (e-ATPase) activity, polymorphonuclear cells, monocytes and various adhesion molecules on the endothelium and the leukocytes. SOD treatment appeared to significantly prevent the increased urinary albumin excretion and the decrease of glomerular e-ATPase activity which were observed in endotoxin-treated rats. This effect of SOD treatment after endotoxin infusion was associated with a significant inhibition of glomerular monocyte influx and a significant inhibition of adhesion molecule expression (glomerular ICAM-1 and VCAM-1 and leukocyte LFA-1 and VLA-4). The present data suggest that in the endotoxin-infused pregnant rat, production of superoxide in the first few hours after the infusion plays a role in the induction of glomerular damage, leading to albuminuria and diminished e-ATPase expression during the following days.

Adenosine Triphosphatases↗
PubMed1997

Plasma endothelin-1 and tumor necrosis factor-alpha concentrations in pregnant and cyclic rats after low-dose endotoxin infusion.

Plasma endothelin-1 and tumor necrosis factor-alpha were determined in pregnant and cyclic rats after infusion of either endotoxin (1.0 microgram/kg of body weight) or saline solution. After endotoxin, but not after saline solution, administration there was a transient endothelin-1 response in pregnant rats but not cyclic rats. In both reproductive conditions there was an equally high transient tumor necrosis factor-alpha response after endotoxin.

Animals↗
PubMed1997

Aspirin treatment of the low-dose-endotoxin-treated pregnant rat: pathophysiologic and immunohistologic aspects.

In the present study, we evaluated the effect of low-dose aspirin (acetylsalicylic acid (ASA); 1.0 mg/kg daily) on blood pressure, albumin excretion, glomerular fibrinogen deposits, and glomerular (basement) membrane-bound adenosine diphosphatase (ecto-ADPase) activity, as well as on glomerular inflammation in pregnant rats infused with low-dose endotoxin (1.0 mg/kg). Rats (day 14 of pregnancy) were infused with endotoxin (ET rats) or saline (control rats) and received ASA in their drinking water. These rats were compared with non-ASA-treated rats. Blood pressure and albumin excretion were measured from day 15 to day 21, and glomerular fibrinogen and ecto-ADPase activity were measured at day 21. Glomerular inflammation was evaluated at various times after the start of the infusion. The results show that treatment with ASA had a significant beneficial effect on hypertension and inflammation induced by endotoxin in pregnant rats, whereas it reduced albumin excretion and glomerular fibrinogen deposits in some of the rats.

Albuminuria↗
PubMed1997

Reproductive condition and the low-dose endotoxin-induced inflammatory response in rats. Glomerular influx of inflammatory cells and expression of adhesion molecules.

These experiments were designed to study the increased sensitivity of pregnant rats to endotoxin. Pregnant (Pr), cyclic (C), and progesterone (P)-treated pseudopregnant rats with or without a decidualized uterus (PSP and DEC rats, respectively) received infusions of an ultra-low dose of endotoxin (1.0 microg/kg BW) and were killed 3 days later. Pr, PSP, and DEC rats were infused on Day 14, C rats on diestrus. Endotoxin-infused rats were compared with saline-infused rats in the same reproductive conditions. The inflammatory reaction of the glomeruli of the kidneys was studied by immunohistochemical methods using 4-microm cryostat sections stained with specific monoclonal antibodies against neutrophils (polymorphonuclear cells, PMNs) and monocytes (MOs), and against the adhesion molecules ICAM-1 and VCAM-1 on the endothelium, and LFA-1, MAC-1, and VLA-4 on the leukocytes. Endotoxin infusion increased glomerular PMN and MO number in Pr, PSP, and DEC rats, all of which have elevated P levels, but not in C rats, which do not. The endotoxin-induced expression of adhesion molecules, associated with this influx of inflammatory cells, varied with the reproductive condition. In C rats there was no increased adhesion molecule expression after endotoxin treatment, in Pr rats there was increased expression of both the combinations ICAM-1/LFA-1 and VCAM-1/VLA-4. DEC rats did not express either of these combinations (although there was expression of ICAM-1); PSP rats expressed the combination ICAM-1/MAC-1. Adhesion molecule expression thus seems to be regulated by ovarian (e.g., P) and placental factors (e.g., of trophoblastic and decidual origin). Because the different combinations of adhesion molecules in the various reproductive conditions after exposure to endotoxin led to more or less the same leukocyte influx under these conditions, the increased sensitivity to endotoxin of pregnant individuals cannot be reduced to differences in leukocyte influx into the glomeruli.

Animals↗
PubMed1997

Modulation of glomerular ECTO-ADPase expression by oestradiol. A histochemical study.

The effect of 17-beta-oestradiol (OE2) upon the activity of the glomerular anti-thrombotic ecto-enzyme ADPase was studied in cyclic and ovariectomized (OVX) Wistar rats. On day 0 (i.e. at the time of ovariectomy or 11 days after ovariectomy) rats received OE2-releasing Silastic implants or empty implants and were sacrificed on day 3, 10 or 21. Cryostat kidney sections were histochemically stained for ecto-ADPase activity using enzyme-histochemistry and glomerular reaction product was quantitatively evaluated by computerized image analysis. Both the histological distribution of reaction product in each glomerulus, as reflected by the relative glomerular area covered with reaction product, as well as enzyme activity, as reflected by staining intensity of the reaction product, were scored. The results show significantly decreased histological distribution after OVX; OVX, however, did not change enzyme activity. It further appeared that OE2 (partly) prevented the decrease of histological distribution in OVX rats, while the enzyme activity was significantly increased by exogenous OE2. In cyclic rats, OE2 did not change histological distribution, although OE2 significantly increased enzyme activity in these rats. It is concluded that glomerular ecto-ADPase expression in the rat kidney is influenced by one or more ovarian factor(s), a very likely candidate being oestradiol. These results may thus point to a dual action of OE2 upon haemostasis: In addition to the known enhancement of procoagulatory plasma factors by OE2, also anti-aggregatory effects may be stimulated by OE2 as reflected by upregulation of vessel wall associated ecto-ADPase activity.

Analysis of Variance↗