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P A Henricks

Publications and source records attributed to P A Henricks.

At least 73 records · Page 4Linked to original sources
PubMed1989

Beta-endorphin and related peptides suppress phorbol myristate acetate-induced respiratory burst in human polymorphonuclear leukocytes.

In the present study, the immunomodulatory effect of beta-endorphin (beta-E) and shorter pro-opiomelanocortin (POMC) fragments was evaluated by assessing their influence on respiratory burst in human polymorphonuclear leukocytes (PMN). The effect of the peptides (10(-17)M - 10(-10)M) on phorbol myristate acetate (PMA)-stimulated production of reactive oxygen metabolites was measured in a lucigenin-enhanced chemiluminescence (CL) assay. Both POMC peptides with opiate-like activity (i.e. alpha-endorphin (alpha-E), beta-E and gamma-endorphin (gamma-E] and their non-opioid derivatives (i.e. des-TYR1-beta-endorphin (dT beta E), des-TYR1-gamma-endorphin (dT gamma E), and des-ENK-gamma-endorphin (dE gamma E] were tested. With the exception of alpha-E, PMA-stimulated respiratory burst was suppressed by all POMC fragments tested. A U-shaped dose-response relation was observed. Doses lower than 10(-17)M and higher than 10(-8)M were without effect. beta-E and dT beta E both suppressed PMA-induced oxidative burst in human PMN at physiological concentrations (10(-16)M - 10(-10)M). gamma-E and dT gamma E proved to be less potent inhibitors, reaching maximal effect at higher concentrations (10(-12)M - 10(-10)M). DE gamma E exerted an even less pronounced but still significant suppressive effect at the concentration of 10(-10)M. None of the endorphins tested was shown to affect resting oxidative metabolism in the PMN. The modulatory effects of the opioid peptides could not be blocked by the opioid antagonist naloxone (10(-8)M). These data show that fragments derived from the POMC-precursor molecule modulate the activation of PMN by suppressing PMA-stimulated oxidative metabolism and that this activity does not involve a classical opiate-like receptor.

Endorphins↗
PubMed1989

Inverse relationship between superoxide anion production of guinea pig alveolar macrophages and tracheal beta-adrenergic receptor function; influence of dietary polyunsaturated fatty acids.

It was shown recently that dietary linoleic acid could modulate beta-adrenergic receptor function in guinea pig tracheal spirals (Loesberg, Folkerts & Nijkamp. Prostagland. Leukotr. essen. Fatty Acids, in press). In the present study the relationship between beta-adrenergic receptor function and oxygen radical production was examined by analyzing the effect of dietary linoleic acid (3, 6 and 12 energy%) on superoxide anion production of guinea pig alveolar macrophages and on relaxation of tracheal spirals upon beta-adrenergic receptor stimulation. An additional dietary group receiving fish oil (3 energy%) in addition to 3 energy% linoleic acid was also included in this study. The zymosan-stimulated (but not the basal) superoxide anion production of the alveolar macrophages differed between the dietary groups. Highest superoxide production was found in those diets that showed the greatest deterioration of beta-adrenergic receptor function. Moreover, a highly significant positive correlation was demonstrated between the amount of generated superoxide and the severity of the attenuation of the beta-adrenergic receptor function in the individual animals. These data suggest that optimal dietary conditions could lead to an improved lung function possibly via modulation of alveolar macrophage radical production.

Animals↗
PubMed1988

Specific and non-specific effects of beta-adrenoceptor agonists on guinea pig alveolar macrophage function.

The existence of beta-adrenoceptors on guinea pig alveolar macrophage membranes was determined by means of radioligand binding studies. Saturable binding with [125I]cyanopindolol demonstrated 38 +/- 6 fmol binding sites per 10(6) alveolar macrophages with a Kd of 0.85 +/- 0.15 nM. With timolol, atenolol and ICI 118.551 for competition of [125I]cyanopindolol binding it became clear that guinea pig alveolar macrophages possessed adrenergic binding sites of the beta 2-subtype. The cyclic AMP levels of alveolar macrophages could be increased by selective beta 2-adrenoceptor agonists but not by selective beta 1-adrenoceptor agonists. The influence of non-selective beta- and selective beta 1- and beta 2-adrenoceptor agonists on the phagocytic and metabolic responsiveness of alveolar macrophages was also studied. Addition of beta-adrenoceptor agonists had no effect on the uptake of bacteria by alveolar macrophages. Incubation of alveolar macrophages with increasing amounts of non-selective and selective beta 1-agonists resulted in a dose-dependent decrease in the detection of hydrogen peroxide released by alveolar macrophages. This effect was due to the scavenging properties of these drugs. The selective beta 2-receptor agonists, salbutamol and terbutaline, had no effect on the oxidative metabolism of alveolar macrophages. We conclude that guinea pig alveolar macrophages possess beta 2-adrenoceptors on their cell surface and that these receptors are not involved in the phagocytic activity of alveolar macrophages.

Adrenergic beta-Agonists↗
PubMed1988

Endotoxin-induced inflammation and injury of the guinea pig respiratory airways cause bronchial hyporeactivity.

It was investigated whether an endotoxin-induced airway inflammation and injury correlated with the induction of bronchial hyperreactivity. Guinea pigs were treated with an endotoxin aerosol, and 4 and 24 h later lung lavages were performed and a differential cell count was made. The number of neutrophils and monocytes was significantly increased (p less than 0.005) at these times. After 24 h, the number of eosinophils and lymphocytes was also increased (p less than 0.005). The number of alveolar macrophages remained unchanged. Histologic examination revealed increased intraluminal mucus and an influx of erythrocytes and neutrophils in the tracheal and bronchial lumen at both time points after the endotoxin aerosol. The epithelium was morphologically changed and contained many neutrophils. Focal matting and/or loss of cilia also occurred. Airway smooth muscle responsiveness was measured in vitro on isolated guinea pig tracheal smooth muscle preparations 4 and 24 h after endotoxin aerosol. No differences in the maximal responses or slope factors of the dose-response curves for carbachol, histamine, or isoprenaline were detected between the control and endotoxin-exposed groups. The EC50 value of the histamine dose-response curve 4 h after endotoxin nebulization was slightly but significantly (p less than 0.05) increased, indicating decreased sensitivity. Responsiveness in vivo was measured in anesthetized spontaneously breathing guinea pigs 24 h after the endotoxin aerosol. The histamine-induced increase in pulmonary resistance was reduced by about 35% in the endotoxin-nebulized group (p less than 0.01). It can be concluded that an influx of inflammatory cells accompanied by injury of the airways induces hyporeactivity of the guinea pig respiratory tract.

Aerosols↗
PubMed1987

Stress diminishes infiltration and oxygen metabolism of phagocytic cells in calves.

The influences of a stress situation on the phagocytic cell function before and after infection with Pasteurella haemolytica were measured in calves. No differences in phagocytic and metabolic activity of alveolar macrophages (AMs) were observed in vitro between cells isolated from stressed and nonstressed animals. The uptake of bacteria and the migration of polymorphonuclear leukocytes (PMNs) did not differ. However, the production of superoxide by PMNs isolated from stressed animals was significantly diminished as compared to control PMNs. The stressed and six of the nine control calves were then infected intrabronchially with P. haemolytica. Phagocytic cell function was again evaluated after three days. The lavage fluid obtained from the lungs of the infected animals contained about three times more PMNs and six times more AMs as compared to the lavage fluid of the control calves. However, the increase in phagocytic cell numbers was less by half in the calves infected after the stress period. No differences were detected in phagocytic and metabolic activity of PMNs and AMs among control, infected, and stressed and infected calves. However, the chemotactic activities of PMNs obtained from infected stressed and infected nonstressed animals were diminished as compared to control PMNs. In conclusion, the metabolic responsiveness of PMNs is diminished and the accumulation of phagocytic cells at a site of infection is reduced after a stress period.

Animals↗
PubMed1987

Phagocytosis and metabolism of alveolar macrophages of guinea pigs treated with Haemophilus influenzae.

Previously we showed that guinea pig alveolar macrophages (AMs) incubated with serum obtained from Haemophilus influenzae-treated animals had detrimental effects on airway smooth muscle beta-adrenergic receptor function. In the present study the influence of H. influenzae treatment on several functions of guinea pig AMs was examined. Sera obtained from animals 4 days after intraperitoneal administration of H. influenzae or from control guinea pigs possessed similar opsonic capacities. No effects of these sera on hydrogen peroxide release by AMs were observed as compared to the basal hydrogen peroxide release of AMs. Interestingly, stimulation of AMs with serum from control animals resulted in a diminished cyclo-oxygenase product formation, which was potentiated after incubating AMs with serum from H. influenzae-treated guinea pigs. No differences in phagocytic activity of AMs isolated from control or H. influenzae-treated animals were observed. When AMs were incubated with phorbol myristate acetate or zymosan, the cells produced superoxide anion and released hydrogen peroxide. However, the amounts of superoxide and hydrogen peroxide released did not differ between AMs isolated from control or H. influenzae-treated animals.

Animals↗
PubMed1986

Human polymorphonuclear leukocytes release leukotriene B4 during phagocytosis of Staphylococcus aureus.

We studied release of leukotriene B4 (LTB4) by human polymorphonuclear leukocytes (PMNs) during phagocytosis of staphylococci in the presence or absence of arachidonic acid. The 12 X 10(7) PMNs incubated with 3 X 10(9) opsonized S. aureus and 50 microM arachidonic acid released 1.45 +/- 0.42 nmol LTB4. No LTB4 was detected after stimulation of PMNs with S. aureus or arachidonic acid by themselves. However, by increasing the concentration of arachidonic acid to 200 or 400 microM, 1.22 +/- 0.45 and 1.98 +/- 0.49 nmol LTB4, respectively, was released by PMNs. The effect of different bacteria-PMN ratios on LTB4 production was also studied. LTB4 varied from 0.3 to 2.0 nmol when bacteria/PMN ratios increased from 5 to 50 (respectively) in the presence of 50 microM arachidonic acid. Thus, phagocytizing PMNs produce LTB4 in the presence of arachidonic acid, and its production is dependent on the number of bacteria phagocytized.

Arachidonic Acids↗
PubMed1986

Modulation of phagocytic cell function.

Phagocytosis is an important factor in the defense of the host against all kinds of microorganisms. The process of phagocytosis of microorganisms by phagocytes can be separated into distinct but interrelated phases: adherence, chemotaxis, opsonization, attachment, ingestion, degranulation and killing. Phagocytosis is accompanied by an increase in oxygen metabolism in which H2O2 and activated oxygen species are generated. Modulation of phagocytic cell function can be brought about by a variety of substances. Microorganisms produce and contain components which influence the process of phagocytosis. Surrounding tissue cells and the phagocytes themselves produce biologically active molecules that modulate phagocytosis.

Arachidonic Acids↗
PubMed1985

Interactions between human polymorphonuclear leukocytes and influenza virus.

The effects of influenza virus A (H3N2) on several functions of human polymorphonuclear leukocytes (PMN) were examined. Incubation of PMN with virus induced chemiluminescence, aggregation, and degranulation of the leukocytes. The amount of chemiluminescence generated increased from 1 X 10(6) to 6 X 10(6) cpm when 2.5 X 10(6) to 2 X 10(7) virus particles were added to 2.5 X 10(6) PMN. Maximal aggregation occurred within 2 min and the response depended on the amount of virus added to the PMN. Release of acid phosphatase by virus-treated PMN was 62 +/- 12% within 1 h compared with 7 +/- 7% by control PMN (P less than 0.005). Incubation of PMN with influenza virus resulted in a diminished phagocytic activity of the phagocytes. PMN from a patient with chronic granulomatous disease were similarly affected. It was thus concluded that the observed defect in phagocytic activity was not due to the reactive oxygen species generated by the PMN during incubation with virus.

Cell Aggregation↗
PubMed1984

Differences in the effect of arachidonic acid on polymorphonuclear and mononuclear leukocyte function.

Incubation of human polymorphonuclear leukocytes with arachidonic acid resulted in a stimulation of the oxidative metabolism of the cells. Upon stimulation with 80 microM arachidonic acid, neutrophils (5 X 10(6) cells/ml) produced superoxide (53 +/- 8 nmol/5 X 10(6) cells per 15 min), generated chemiluminescence (1211 100 +/- 157 000 cpm) and consumed oxygen (20 +/- 1 nmol/10(6) cells per 5 min). The stimulation of the cell metabolism could be reduced 40-60% by prior incubation of the cells with 10 microM indomethacin. Incubating polymorphonuclear leukocytes with arachidonic acid also resulted in a diminished chemotaxis towards an attractant, a decreased uptake of opsonized staphylococci and aggregation of the cells. This may be due to inhibitory products of arachidonic acid metabolism and toxic oxygen species produced during stimulated oxidative metabolism. The effects of arachidonic acid are specific for neutrophils, as mononuclear phagocytes only produced 17 +/- 8 nmol superoxide/5 X 10(6) cells per 15 min and generated 27 000 +/- 15 000 cpm chemiluminescence when stimulated with 80 microM arachidonic acid. When monocytes and neutrophils were stimulated with particles such as opsonized staphylococci, the amount of superoxide produced, oxygen consumed and chemiluminescence generated were similar. The phagocytic activity of the monocytes was also not affected by prior incubation with arachidonic acid. We conclude that in contrast to monocytes, neutrophil metabolism can be stimulated with arachidonic acid and this stimulation resulted in a decreased phagocytic activity of these cells.

Arachidonic Acid↗
PubMed1984

Aggregation of human polymorphonuclear leucocytes during phagocytosis of bacteria.

The process of aggregation of human polymorphonuclear leucocytes (PMN) during the uptake of bacteria was studied. Radiolabelled S. aureus were opsonized in different sera, washed, resuspended in buffer and added to the PMN. Uptake of the bacteria and aggregation of the PMN were measured simultaneously. Maximal aggregation occurred within 6 min, when 5 X 10(6) PMN had phagocytosed 2.5 X 10(8) S. aureus. Also the effects of serum concentrations and different sera for opsonization of the bacteria on PMN aggregation were studied. Despite normal uptake, aggregation of PMN was low when bacteria were opsonized in complement-deficient sera. Furthermore when PMN were treated with pronase to inactivate complement receptors on the cell surface of the PMN, and bacteria preopsonized in immune serum were added, no change in uptake occurred, although the degree of aggregation halved compared to control PMN. So, interaction between the bacteria and the complement receptor of the PMN cell membrane is needed for triggering the process of aggregation. By using dansylcadaverin and diphenylamine to modulate lysosomal enzyme release, azide or PMN from a chronic granulomatous disease patient to study the effect of the formation of oxygen species, and theophylline, DB-cAMP or 8 Br-cAMP to increase cAMP levels, it was concluded that aggregation of PMN during phagocytosis was not dependent on oxygen metabolism, degranulation or cAMP levels of PMN.

Adult↗