Biomedical subjects

F A Moore

Publications and source records attributed to F A Moore.

At least 55 records · Page 3Linked to original sources

PubMed1997

Reduced PAF-acetylhydrolase activity is associated with postinjury multiple organ failure.

Our basic laboratory work has identified the postischemic gut as a source of platelet-activating factor (PAF), which primes circulating neutrophils for the production of reactive oxygen metabolites (ROMs) leading to distant organ injury. Circulating PAF-acetylhydrolase (PAF-AH) hydrolyzes PAF to lyso-PAF. Recently, ROMs have been shown to rapidly and irreversibly inactivate human PAF-AH. Consequently, our study hypothesis was that reduced levels of PAF-AH in severely injured patients would be associated with the development of multiple organ failure (MOF). Over a 16 mo period, 26 patients at known risk for MOF (Injury Severity Score (ISS) > or = 25 or an ISS > 15 with > or = 6 U of blood transfused within the first 6 h) had blood sampled on postinjury days 0, 1, 2, 3, and 5. PAF-AH activity was assessed by measuring the percentage of 3H-labeled PAF hydrolyzed. MOF was defined by a standard score. The mean age of the 26 study patients was 34 +/- 2 yr; 19 (73%) were male. The injury mechanism was blunt in 18 (69%), and the mean ISS was 31 +/- 2. Eight patients (31%) developed MOF. In the MOF patients, plasma PAF-AH activity was significantly lower on the day of injury and remained depressed throughout the ensuing 5 days compared with the non-MOF patients. Reduced PAF-AH activity is associated with the development of postinjury MOF. With the recent molecular cloning of human plasma PAF-AH, repleting this circulating, anti-inflammatory enzyme may represent useful therapy for these high risk patients.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1997

Serum ferritin as a predictor of the acute respiratory distress syndrome.

We investigated serum ferritin levels as a predictor of the acute respiratory distress syndrome (ARDS) because: (1) proinflammatory cytokines, which are implicated in ARDS, increase ferritin synthesis; and (2) oxidative stress in patients at risk for ARDS might liberate iron from ferritin, accelerating toxic hydroxyl radical (.OH) formation. Serum ferritin levels measured by radioimmunoassay (RIA) were greater in 75 patients at risk for ARDS (women, p < 0.0001; men, p < 0.0001) and 8 patients with ARDS (women, p = 0.001; men, p = 0.0009) than in healthy control subjects. Serum ferritin levels were also greater in female (p = 0.003) and male (p = 0.003) at-risk patients who developed ARDS than in patients who did not develop ARDS. In women, a value exceeding 270 ng/ml predicted ARDS with an 83% sensitivity, 71% specificity, 67% positive, and 86% negative predictive value. In men, a value exceeding 680 ng/ml predicted ARDS with a 60% sensitivity, 90% specificity, 75% positive, and 82% negative predictive value. Serum ferritin levels did not correlate with C-reactive protein levels, were not different in medical or surgical at-risk patients, and were not accounted for by liver disease. Evaluating serum ferritin levels in at-risk patients may help predict the development of ARDS and thereby improve study and treatment of ARDS. Elevated serum ferritin levels may also regulate the participation of iron in the oxidative responses that contribute to ARDS.

Adult↗

PubMed1997

Circulating IL-1ra and IL-10 levels are increased but do not predict the development of acute respiratory distress syndrome in at-risk patients.

Although numerous cytokines, including interleukin (IL)-1, IL-8, and tumor necrosis factor, circulate in critically ill patients at risk for acute respiratory distress syndrome (ARDS), none clearly predict the development of the syndrome. We hypothesized that cytokines, such as IL-1ra, IL-10, and IL-4, which modulate inflammation, might contribute to or reflect the development of acute lung injury. Accordingly, serial levels of IL-1ra and IL-10 were measured in 77 patients who were identifed as being at risk for the development of ARDS. Initial IL-1ra levels were significantly higher (p < 0.0001) in the patients (7.82 [2.29-38.01] ng/ml) than in normal control subjects (0.24 [0.24-0.34] ng/ml) but did not predict the development of ARDS. Initial IL-1ra levels, however, were greater (p = 0.038) in the patients who died (31.95 [3.02-65.06] ng/ml) compared with survivors (6.61 [1.86-29.33] ng/ml). Similarly, IL-10 levels were increased in patients (155 [53.75-318.75] ng/ml) compared with normal control subjects (0 ng/ml) but did not predict the development of ARDS. Like IL-1ra levels, initial IL-10 levels were significantly higher (p = 0.005) in patients who died compared with survivors. IL-4 was not detectable in any of the patient plasma samples measured. Thus, modulators of inflammation are increased in patients at risk for ARDS who die, but do not predict the development of the syndrome.

Adult↗

PubMed1997

Blood transfusion. An independent risk factor for postinjury multiple organ failure.

OBJECTIVE: To determine if blood transfusion is a consistent risk factor for postinjury multiple organ failure (MOF), independent of other shock indexes. DESIGN: A 55-month inception cohort study ending on August 30, 1995. Data characterizing postinjury MOF were prospectively collected. Multiple logistic regression analysis was performed on 5 sets of data. Set 1 included admission data (age, sex, comorbidity, injury mechanism, Glasgow Coma Scale, Injury Severity Score, and systolic blood pressure determined in the emergency department) plus the amount of blood transfused within the first 12 hours. In the subsequent 4 data sets, other indexes of shock (early base deficit, early lactate level, late base deficit, and late lactate level) were sequentially added. Additionally, the same multiple logistic regression analyses were performed with early MOF and late MOF as the outcome variables. SETTING: Denver General Hospital, Denver, Colo, is a regional level I trauma center. PATIENTS: Five hundred thirteen consecutive trauma patients admitted to the trauma intensive care unit with an Injury Severity Score greater than 15 who were older than 16 years and who survived longer than 48 hours. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The relationship of blood transfusions and other shock indexes with the outcome variable, MOF. RESULTS: A dose-response relationship between early blood transfusion and the later development of MOF was identified. Despite the inclusion of other indexes of shock, blood transfusion was identified as an independent risk factor in 13 of the 15 multiple logistic regression models tested; the odds ratios were high, especially in the early MOF models. CONCLUSIONS: Blood transfusion is an early consistent risk factor for postinjury MOF, independent of other indexes of shock.

Adolescent↗

PubMed1997

Pulmonary contusion: are children different?

BACKGROUND: Pulmonary contusion (PC) is a common sequelae of blunt trauma in adults and children; previous reports suggest that children have more favorable outcomes because of differences in mechanisms of injury, associated injury, and physiologic response. Our objective was to determine whether children who sustain PC have different outcomes compared with similarly injured adults. STUDY DESIGN: Our Level I Trauma Registry was reviewed for a 4-year period and identified 251 consecutive patients who sustained PC. Their charts were reviewed retrospectively for demographics, injury mechanism, injury severity scores, associated injuries, and outcomes (measured by the need for intubation, ventilation days, pneumonia, acute respiratory distress syndrome, and death). Data are expressed as the mean +/- SEM. The Student's t-test was used to compare the groups. A p value less than 0.05 was considered significant. RESULTS: Of the study patients, 41 (16%) were children (ages 2-16, mean 10 years) and 210 (84%) were adults (ages 17-80, mean 34 years). The most common injury mechanisms in children were motor vehicle accidents (56%) and auto-pedestrian accidents (39%), but in adults, motor vehicle accidents (80%, p = 0.02) predominated. Injury severity score was not significantly different between groups (children, 26 +/- 2 and adults 25 +/- 1). Similarly, the incidence of associated injuries was not different between children and adults: head 78% versus 62%, abdomen 59% versus 43%, and skeletal fractures 41% versus 29%, respectively. Neither need for intubation, ventilator days, pneumonia, acute respiratory distress syndrome, or death differed significantly between groups. CONCLUSIONS: Although children and adults differ in regard to injury mechanism, their overall injury severity, associated injuries, and outcomes are quite similar. Thus, contrary to previous reports, children do not have a more favorable outcome after PC.

Accidents, Traffic↗

PubMed1996

The role of chronic alcohol abuse in the development of acute respiratory distress syndrome in adults.

OBJECTIVE: To determine the effect of a history of chronic alcohol abuse on the incidence of acute respiratory distress syndrome (ARDS) and in-hospital mortality. DESIGN: Prospective cohort study. PATIENTS: A total of 351 medical and surgical intensive care unit patients with one of seven at-risk diagnoses for the development of ARDS. MAIN OUTCOME MEASURES: The development of ARDS and in-hospital mortality. RESULTS: Of the 351 patients enrolled in the study, the incidence of ARDS in patients with a history of alcohol abuse was significantly higher than in patients without a history of alcohol abuse (43% vs 22%) (P < .001; relative risk [RR], 1.98; 95% confidence interval [Cl], 1.32 to 2.85). In patients with sepsis, ARDS developed in 52% of the patients with a prior history of alcohol abuse compared with only 20% in patients without a history of alcohol abuse (P < .001; RR, 2.59; 95% Cl, 1.29 to 5.12). Fifty-one percent (52/102) of the patients who developed ARDS died compared with only 14% (36/249) of patients who did not develop ARDS (P < .001). In the subset of patients who developed ARDS, the in-hospital mortality rate was 65% in patients with a prior history of alcohol abuse. This mortality rate was significantly higher (P = .003) than the mortality rate in patients without a history of alcohol abuse (36%). CONCLUSIONS: A prior history of chronic alcohol abuse significantly increases the risk of developing ARDS in critically ill patients with an identified at-risk diagnosis. Our results may be useful in the earlier and more accurate identification of patients at high risk for developing ARDS.

APACHE↗

PubMed1996

Interleukin-6 delays neutrophil apoptosis.

BACKGROUND: Neutrophil (PMN) apoptosis promotes the phagocytosis of PMNs without inciting an inflammatory response or local cytotoxic effect. This is important in the normal resolution of inflammatory processes and the control of tissue injury. Conversely, a delay in PMN apoptosis may facilitate PMN-mediated organ dysfunction by extending PMN functional integrity at an inflammatory site. Elevated circulating and tissue levels of interleukin-6 (IL-6) have been associated with postinjury organ dysfunction, and IL-6 appears to augment PMN cytotoxic functions. Therefore, we hypothesized that IL-6 delays PMN apoptosis, thereby enhancing PMN-mediated cytotoxicity. METHODS: Neutrophils isolated from healthy human donors were incubated for 24 hours in enriched RPMI 1640 cell culture medium at 37 degrees C in 5% carbon dioxide. Subgroups were incubated with IL-6, heat-denatured IL-6, or buffer alone. Apoptosis was assessed morphologically using acridine orange-ethidium bromide stain, and biochemically by DNA gel electrophoresis. Functional capacity of PMNs was assessed by superoxide generation after activation with phorbol myristate acetate or platelet-activating factor plus formyl-methionyl-leucyl-phenylalanine. RESULTS: Treatment with IL-6 resulted in a greater population of surviving (nonapopototic) PMNs after 24 hours. In addition, the IL-6-treated population produced more superoxide after 24 hours than did the untreated or heat-denature IL-6-treated groups, after either activating stimulus. CONCLUSIONS: Interleukin-6 delays PMN apoptosis, resulting in a larger population of surviving PMNs with a greater collective capacity for superoxide production. This could potentially facilitate PMN-mediated tissue injury and may be a mechanism whereby IL-6 contributes to organ dysfunction.

Apoptosis↗

PubMed1996

Sequential systemic platelet-activating factor and interleukin 8 primes neutrophils in patients with trauma at risk of multiple organ failure.

Plasma from 33 patients at risk of multiple organ failure (MOF) after major trauma was tested for a priming effect on neutrophils, and for the presence of platelet-activating factor (PAF) activity and interleukin (IL) 8. Plasma sampled at 3, 6, 12 and 24 h after injury significantly primed normal neutrophils to release mean(s.e.m.) 1.26(0.19), 1.33(0.26), 1.04(0.14) and 0.86(0.13) nmol superoxide per min per 1.3 x 10(6) neutrophils respectively (P < 0.05). Priming at 3 h after injury was inhibited by mean(s.e.m.) 63.8(7.0) per cent by the PAF antagonist, WEB 2170 (P < 0.01). Mean(s.e.m.) plasma IL-8 was raised at 6 and 12 h after injury to 785(183) and 836(175) pg/ml (P < 0.01). At 12 h after injury the plasma IL-8 level correlated directly with the number of units of red blood cells transfused (r = 0.64, P < 0.01), and was significantly higher in the group of six patients who developed MOF (P < 0.05). These data suggest that after trauma the mediators PAF and IL-8 appear sequentially in the circulation, are potential mechanisms of circulating neutrophil priming, and that IL-8 may also be an early biochemical marker predicting the onset of MOF.

Adolescent↗

PubMed1996

Interleukin-6 stimulates neutrophil production of platelet-activating factor.

Interleukin-6 (IL-6) is an integral mediator of the acute phase response to injury and infection; an exaggerated IL-6 response has been associated with adverse clinical events. The precise role of IL-6 is unclear, but it appears capable of modulating the functional repertoire of mature neutrophils (PMNs). Our previous work demonstrated that IL-6 -stimulated PMNs are primed by lower concentrations of platelet-activating factor (PAF) than nonstimulated PMNs. Recently, we have found that IL-6 suppresses PMN apoptosis via a PAF-like mechanism. We hypothesized that IL-6 stimulates PMNs to produce PAF. PMNs isolated from healthy human donors were incubated with IL-6 (0.1-100 ng/ml) at 37 degrees C. Lipid production was measured by use of thin-layer chromatography, and PAF quantitated with a scintillation proximity assay. IL-6 (1 and 10 ng/ml) stimulated PMNs to produce increase quantities of PAF. PAF production was associated with an increase in PMN cytosolic calcium. These data may provide mechanistic insight into IL-6 regulation of PMN-mediated cytotoxicity and the role of PAF in mediating IL-6 effects on PMNs.

Amino Acid Sequence↗

PubMed1996

Hypoxia/reoxygenation of human endothelium activates PMNs to detach endothelial cells via a PAF mechanism.

Our previous in vivo studies have implicated phospholipase A2 activation and platelet-activating factor (PAF) production as an important mediator of neutrophil (PMN) priming after mesenteric ischemia/reperfusion. Furthermore, our in vitro studies demonstrate that PAF priming of PMN enhances PMN respiratory burst and increases PMN adherence to human umbilical vein endothelial cell cultures (HUVEC). Others have shown that cytokine stimulated HUVEC can activate quiescent PMNs to provoke endothelial cell (EC) monolayer disruption via EC detachment by a noncytolytic PMN protease mechanism. Hypoxia and reoxygenation (H/R) of HUVEC can also directly stimulate PAF production. Consequently, we hypothesized that HUVEC H/R can activate quiescent PMNs to disrupt the EC monolayer (detachment) through a PAF mediated mechanism. HUVEC were labeled with 51 chromium (51Cr) and subjected to 45 min hypoxia (95% N2/5% CO2). PMNs freshly isolated by Percoll gradient centrifugation were added to HUVEC and reoxygenated for 120 min. Additionally, H/R HUVEC with PMN pretreated with WEB2170 (a PAF receptor antagonist) was compared to control (non-H/R HUVEC incubated with PMNs). Wells were washed at end incubation, and adherent ECs counted. Detachment = [total counts - sample counts]/total counts X 100. H/R HUVEC plus PMN provoked a 29.3 +/- 1.6% detachment of EC compared to 9.3 +/- 2.9% detachment in control (non-H/R HUVEC with PMNs). In contrast, H/R HUVEC with PMNs preincubated with WEB2170 had 9.9 +/- 3.8% detachment of EC. In summary, HUVEC H/R activated quiescent PMNs to disrupt an EC monolayer (detachment) via a PAF mechanism.

Cell Adhesion↗

PubMed1996

Soluble ICAM-1 (sICAM-1) provokes PMN elastase release.

Elevated levels of soluble intercellular adhesion molecule-1 have been shown predictive of post-injury multiple organ failure. We hypothesized that sICAM-1 augments distant organ injury via its affect on the PMN and; thus, have examined neutrophil elastase and superoxide production in response to sICAM-1. To obtain soluble ICAM-1, Chinese Hamster Ovarian (CHO) cells were transfected with human ICAM-1 (cDNA vector CD1.8), lysed and centrifuged at 150,000g for 1 hr; supernatant was passed over an ICAM-1 affinity gradient, eluted with 0.1 mM glycine x HCl, and concentrated using an Amicon Spin-X filter. PMNs were incubated for 1 hr with sICAM-1 at 37 degrees C. Quiescent and PMA-activated PMNs served as negative and positive controls respectively. Elastase activity was measured by the cleavage of methoxy-succinyl-alalyl-alalyl-prolyl-valyl-p-nitroanilide. Superoxide production was determined by superoxide dismutase inhibitive ferricytochrome C reduction over a 5-60 min incubation. PMN incubation with sICAM-1 provoked marked increase in elastase release 10.43 +/- 2.90 (10(-6) U/hr) compared to control 1.64 +/- 0.57, and was equivalent to PMA-activated PMN elastase release 11.60 +/- 1.50 (10(-6) U/hr). In contrast, sICAM-1 alone did not promote spontaneous PMN superoxide production beyond buffer treated PMNs (0.25 +/- 0.09 nmole/2.5 x 10(5) PMN/min). In sum, sICAM-1 stimulates PMN elastase release in vitro. Clinically, this may represent a mechanism by which sICAM-1 participates in the genesis of post-injury multiple organ failure.

Amino Acid Sequence↗

PubMed1996

Nitric oxide reduces endothelial expression of intercellular adhesion molecule (ICAM)-1.

Nitric oxide (NO.) has proven effective in improving oxygenation and reducing pulmonary hypertension in the acute respiratory distress syndrome (ARDS), but the precise mechanism remains unclear. NO. has been shown to reduce leukocyte-endothelial adhesion, attenuate neutrophil (PMN) sequestration, and protect endothelium from an inflammatory insult. Intercellular adhesion molecule (ICAM)-1 is a pivotal regulator of PMN-endothelial adhesion and, thus, a critical mediator of PMN cytotoxicity. Consequently, we hypothesized that NO. suppresses ICAM-1 expression on endothelium. Human umbilical vein endothelial cells (HUVEC) were cultured. The NO. donor 3-morpholinosidnonimine (SIN-1) (0.1-10 microM) was incubated with HUVEC for 4 hr. In separate experiments, HUVEC were incubated with bacterial lipopolysaccharide (LPS) (100 ng/ml) alone or following SIN-1 pretreatment. ICAM-1 expression on HUVEC was measured by flow cytometric analysis. SIN-1 (1 and 10 microM) reduced the expression of ICAM-1 on resting HUVEC by 58 and 47%, respectively. LPS upregulated ICAM-1 expression; however, this was not affected by SIN-1 pretreatment. We conclude that NO. reduces constitutive endothelial expression of ICAM-1, but does not prevent LPS-stimulated upregulation of ICAM-1 expression. Downregulation of ICAM-1 may be a mechanism whereby NO. protects resting endothelium (distant organ bed) from circulating primed or activated PMNs, but may not be as effective at a primary inflammatory site.

Analysis of Variance↗

PubMed1996

Early risk factors for postinjury multiple organ failure.

Epidemiologic studies, based on retrospective data from heterogeneous populations with poor control of confounders, led early investigators to conclude that infection was the overriding risk factor for multiple organ failure (MOF). More recent studies have convincingly shown that MOF frequently occurs in the absence of infection. Consequently, we have shifted our research focus away from the traditional infectious models of MOF to the newer "one-hit" and "two-hit" inflammatory models. Clinically, we have chosen to study trauma patients because they are a relatively homogeneous group with a low incidence of common confounders. Trauma also permits a clear distinction between the first insult and the outcome, both temporally and with respect to the definition criteria. In this review we discuss the background, rationale, and our initial attempts to use indicators of the first insult (i.e., tissue injury quantification and clinical signs of shock) and indicators of the host response (i.e., systemic inflammatory response syndrome) to predict MOF early after injury.

Critical Care↗

PubMed1996

Involvement of bradykinin B1 and B2 receptors in human PMN elastase release and increase in endothelial cell monolayer permeability.

Bradykinin (BK) is a potent inflammatory mediator, which can release other inflammatory mediators by interacting with bradykinin B1 and B2 receptors. The role of kinins in regulating human PMN elastase release was studied. BK induced elastase release 5-fold over basal levels. Elastase release was inhibited by both B1 and B2 receptor antagonists. A specific B1 agonist des-Arg10-KD increased elastase release 4-fold. Since elastase has been implicated in vascular leak, the effect of BK on endothelial cell monolayer (EM) permeability was assessed. BK increased EM leak (I125 flux) across the EM, whereas des-Arg10-KD was inactive. When co-cultured with human umbilical vein endothelial cells, des-Arg10-KD-treated PMNs increased EM leak by 35%. The elastase inhibitor AAVPK blocked des-Arg10-KD-induced leak by 80% suggesting that elastase is responsible for the increase in permeability. It is concluded that BK causes increased leak by inducing PMN elastase release via activation of both B1 and B2 receptors. BK blockade and elastase inhibition may be beneficial in inflammatory diseases such as ARDS which is characterized by increased lung permeability and both kinin and PMN activation are thought to participate.

Amino Acid Chloromethyl Ketones↗

PubMed1996

Tracheal gas insufflation is a useful adjunct in permissive hypercapnic management of acute respiratory distress syndrome.

BACKGROUND: Despite numerous advances in critical care, the mortality of postinjury acute respiratory distress syndrome (ARDS) remains high. Recently, permissive hypercapnia (PHC) has been shown to be a viable alternative to traditional ventilator management in patients with ARDS. However, lowering tidal volume, as employed in PHC, below 5 cc/kg impinges upon anatomic dead space and precipitates a significant rise in PaCO2 The purpose of this study was to determine if continuous tracheal gas insufflation (cTGI) is a useful adjunct to PHC by lowering PaCO2, thus allowing adequate reduction in minute ventilation to achieve alveolar protection. METHODS: Over a 5-year period, 68 trauma patients with ARDS were placed on permissive hypercapnia. Nine of these patients additionally received cTGI at 7 L/min. Arterial blood gas determinations and ventilatory parameters were examined immediately prior to the implementation of cTGI and after 6h. RESULTS: The cTGI produced significant improvement in pH (7.25 +/- 0.03 to 7.33 +/- 0.03), PaCO2 (72 +/- 5 to 59 +/- 5 torr), tidal volume (7.9 +/- 0.6 to 7.2 +/- 0.6 cc/kg), and minute ventilation (13 +/- 1 to 11 +/- 1 L/min; P < 0.05). CONCLUSIONS: Continuous TGI is a useful adjunct to permissive hypercapnia, allowing maintenance of an acceptable pH and PaCO2 while allowing further reduction in tidal volume and minute ventilation.

Adolescent↗

PubMed1996

Jack A. Barney Resident Research Award winner. The inflammatory profile of interleukin-6, interleukin-8, and soluble intercellular adhesion molecule-1 in postinjury multiple organ failure.

BACKGROUND: Interleukin-6 (IL-6), interleukin-8 (IL-8), and adhesion molecules have been implicated as mediators in neutrophil (PMN) and endothelial cell (EC) interactions leading to postinjury multiple organ failure (MOF). Our hypothesis was that circulating levels of IL-6, IL-8, and soluble intercellular adhesion molecule-1 (sICAM-1) would discriminate patients at risk for postinjury MOF. METHODS: Serial plasma levels of IL-6, IL-8, and sICAM-1 were measured in 27 high-risk trauma patients. RESULTS: The IL-6 and IL-8 levels were significantly elevated in MOF patients compared with non-MOF patients at 12 and 36 hours postinjury. The IL-6 level was also elevated at 84 and 132 hours, and IL-8 at 84 hours. The sICAM-1 level did not become elevated in MOF patients until 132 hours postinjury. CONCLUSION: Interleukin-6 and IL-8 are elevated early after trauma and discriminate patients who will develop MOF. Late elevation of sICAM-1 likely results from PMN cytotoxicity leading to EC injury or inflammation.

Adult↗

PubMed1996

Soluble intercellular adhesion molecule-1 provokes polymorphonuclear leukocyte elastase release by CD18.

BACKGROUND: Elevated levels of soluble intercellular adhesion molecule-1 (sICAM-1) correlate with the development of postinjury multiple organ failure. Soluble ICAM-1 secretion is known to be induced in endothelial cells and monocytes by diverse inflammatory stimuli. We have found that incubation of quiescent polymorphonuclear leukocytes (PMNs) with sICAM-1 elicits elastase release and, more recently, that cross-linking CD18 receptors on PMNs also produces elastase release. Consequently, our study hypothesis was that sICAM-1 provokes PMN elastase release through its interaction with CD18. METHODS: To obtain sICAM-1, Chinese hamster ovarian cells transfected with human ICAM-1 were lysed and centrifuged at 150,000 g for 1 hour; the supernatant was passed over an ICAM-1 affinity column, eluted with 0.1 mmol/L glycine HCl, and concentrated with dialysis filter. Human PMNs (2.5 x 10(5)) were saturated with specific monoclonal antibodies for the beta 2 subunits (CD11a, CD11b, CD18) or nonspecific monoclonal antibodies for 30 minutes on ice before a 1-hour incubation with sICAM-1 (75 ng/ml) at 37 degrees C. Elastase activity was measured by the cleavage of n-methoxysuccinyl-A-A-P-V-p-nitroanilide. RESULTS: Neutrophil incubation with sICAM-1 resulted in 19.2% +/- 2.8% of total PMN elastase, compared with 2.4% +/- 0.5% in the controls. Blockade of CD18 abrogated sICAM-1 provoked elastase release with monoclonal antibodies to CD18 (TS1/18, 31H8) resulting in 4.3% +/- 1.0% and 5.5% +/- 1.4% elastase release, respectively. Blockade of CD11a, CD11b, and nonspecific antibody controls had no effect on sICAM-1 induced elastase release. CONCLUSIONS: In vitro, sICAM-1 provokes PMN elastase release through CD18. This may represent a mechanism by which elevated levels of circulating sICAM-1, released from local injury sites, provoke distal organ dysfunction.

Animals↗

PubMed1996

The abdominal compartment syndrome.

1. ACS is caused by an acute increase in intra-abdominal pressure, usually as a result of intra-abdominal hemorrhage. 2. The most common and significant complications are respiratory and renal failure. 3. Abdominal decompression promptly reverses the complications of ACS. 4. Failure to recognize and treat ACS is inevitably fatal.

Abdomen↗