Improvement of plasma lipoprotein profiles during high-flux dialysis

Patients undergoing maintenance hemodialysis therapy have increased mortality due to cardiovascular disease. One possible etiologic factor for this increased mortality is the lipid abnormalities associated with chronic renal failure. These include elevated triglyceride (TG) and decreased high-density lipoprotein (HDL) concentrations. Lipoprotein profiles of patients undergoing chronic hemodialysis with either saponified cellulose ester (CE) (N = 9) or polysulfone (PS) high-flux dialysis membranes (N = 10) were compared. Patients in each group received similar amounts of heparin during the dialysis. CE-dialyzed patients showed no alteration in serum TG, HDL, low-density lipoprotein, or total cholesterol when predialysis and postdialysis values were compared. PS patients, on the other hand, had a significant decrease in TG concentrations (P < 0.01) as well as a significant rise in HDL (P < 0.01). These changes might signify activation of lipoprotein lipase (LPL) during dialysis. LPL activity in PS sera was significantly greater than LPL in CE sera. Moreover, sera from PS patients inhibited LPL much less than did sera from CE patients. These findings suggest that a circulating substance not dialyzable with cellulosic membranes inhibits LPL in uremic subjects and is removed during dialysis with a PS membrane. Alternatively, the greater biocompatibility of PS may produce less LPL inhibitory cytokines during dialysis. The improvement of lipoprotein profiles in patients receiving dialysis with PS membranes may, in the long term, lead to less morbidity and mortality from atherosclerotic disease.     

Relationship between cleaved L-selectin levels and the outcome of acute myeloid leukemia

High plasma levels of the shed form of L-selectin (sL-selectin) are frequently detectable in acute myeloid leukemia (AML). sL-selectin can inhibit blast cell adhesion to vascular endothelium and may thereby influence the phenotype of AML. In this study, we have investigated the relationship between sL-selectin levels and clinical presentation or disease outcome in 100 patients with AML. Fifty-eight patients were found to have sL-selectin levels >/=3.12 microgram/mL (>/=3 SD above the mean of healthy controls: "increased"). Patients with extramedullary disease such as lymphadenopathies, splenomegaly, hepatomegaly, and/or muco-cutaneous infiltration had significantly increased sL-selectin levels (P < .001). sL-selectin levels were significantly heterogeneous in the French-American-British subtypes (P = .0003). Patients with "normal" sL-selectin levels had higher probability of achieving complete remission (CR) than with "increased" levels: 81% versus 64%, respectively (P = .06). When adjusting for clinically relevant covariates predictive for CR (sex, age, Auer rods), "normal" sL-selectin levels were significantly associated with CR (odds ratio, 3.08; 95% confidence interval [CI], 1.10 to 8.58; P = .03). Moreover, patients with "increased" sL-selectin levels (>/=3.12 microgram/mL) had shorter event-free survival (EFS) (median 7.3 v 12 months, P = .008) and overall survival (median 1 v 2.05 years, P = .03) than patients with sL-selectin <3.12 microgram/mL. Multivariate statistical analysis (adjusted for age and presence of Auer rods) indicated that sL-selectin was an independent prognostic factor for EFS (hazard ratio [HR], 1.96; 95% CI, 1.21 to 3.17, P = .006) and overall survival (HR, 1.80; 95% CI, 1.09 to 2.98; P = .02). Thus, plasma sL-selectin may be a useful prognostic marker in the evaluation of AML at diagnosis.     

Impaired neutrophil function in chronic renal failure--dysregulation of surface adhesion molecule expression and phagocytosis

To elucidate the impaired neutrophil function in patients with chronic renal failure, we analyzed the expression of the adhesion molecules, LAM-1, LFA-1, Mac-1, gp150/95 and phagocytosis activity of neutrophils in predialysis and hemodialysis patients by flow cytometry. Further, the response to granulocyte colony-stimulating factor (G-CSF), N-formyl-methionyl-leucyl-phenylalanine (fMLP) and tumor necrosis factor alpha (TNF alpha) were investigated. In hemodialysis patients, the expression of LAM-1 was decreased and that of MAC-1 was increased, indicating the activation of neutrophils. Also in predialysis patients, the same condition of "low LAM-1, high MAC-1" was observed, but to a lesser degree. Phagocytosis activity was significantly decreased in hemodialysis patients, whereas the neutrophils of predialysis patients showed almost the same phagocytosis activity compared to the controls. The responses to G-CSF, fMLP, TNF alpha were significantly reduced both in hemodialysis and predialysis patients. The inadequate activation of neutrophils and impaired response to stimulation may play an important role in uremic patients with regard to increased susceptibility to infections.     

Preserved antioxidative defense of lipoproteins in renal failure and during hemodialysis

Contact to artificial surfaces during hemodialysis activates leukocytes, which then form oxidized arachidonic acid products and free radicals. This might promote the oxidative modification of low-density lipoproteins (LDL) that play a key role in the initiation of atherosclerosis. Thus, leukocyte activation could specifically contribute to the high mortality from atherosclerotic complications on long-term hemodialysis. Therefore monitored LDL and high-density lipoprotein (HDL) resistance to copper-stimulated oxidation in patients with end-stage renal disease on maintenance hemodialysis with cellulose acetate or polysulfone membranes (n = 12), in patients with chronic renal failure (n = 13) and in healthy controls (n = 12). Six of the dialysis patients were restudied during a single cuprophane dialysis. Circulating leukocytes were reversibly reduced early in hemodialysis with cellulose acetate (minimum, 83.6% +/- 7.4% of baseline values at 30 minutes after dialysis start), polysulfone (minimum, 80.4% +/- 10.5% at 15 minutes; P < 0.05) and cuprophane (minimum, 24.5% +/- 8.5% at 60 minutes; P < 0.0001). Despite the leukocyte activation, LDL oxidation lag time was not shortened in comparison with healthy controls and was even prolonged at the end of cellulose acetate (P < 0.05) and cuprophane (P < 0.05) dialysis. HDL oxidation lag time increased (12.6% +/- 0.9%; P < 0.0001) 15 to 60 minutes after start of hemodialysis and returned to predialysis values thereafter. In patients with chronic renal failure, the lag time of HDL oxidation was significantly prolonged (13.34 minutes +/- 0.9) compared with healthy controls (10.91 +/- 2.0 minutes; P < 0.01) as well as compared with the dialysis patients at baseline (9.9 minutes +/- 1.4; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of an L-selectin ligand on hematopoietic progenitor cells

The process of hematopoiesis is dependent on discrete cell-cell and cell-matrix interactions which are tightly regulated by expression of adhesion molecules. L-selectin, an adhesion protein best known for regulating leukocyte attachment to endothelium, is characteristically expressed on the earliest hematopoietic progenitor cells. Ligands for L-selectin have been extensively characterized on endothelial cells. We recently identified a ligand for L-selectin expressed on the human hematopoietic progenitor cell line KG1a. This molecule is an integral membrane glycoprotein which is structurally different from all ligands previously described. We hypothesize that this molecule may mediate L-selectin-specific adhesive interactions during hematopoiesis. This article discusses the biology of L-selectin and its ligands, and reviews our current understanding of the structure and distribution of the L-selectin ligand expressed on hematopoietic cells.     

L-selectin crosslinking induces integrin-dependent adhesion: evidence for a signaling pathway involving PTK but not PKC

L-selectin mediates the initial contact of leukocytes with the endothelium prior to extravasation. Here we demonstrate that L-selectin engagement can induce rapid and avid integrin-dependent T cell adhesion to recombinant immobilized cell adhesion molecules (CAMs) including ICAM-1, ICAM-3, and VCAM-1, as well as to the extracellular matrix protein fibronectin (FN). L-selectin-induced adhesion to these integrin ligands shares characteristics with CD3 mAb- or phorbol ester-induced adhesion in requiring metabolic energy, tyrosine kinase and ligand-stimulated Ca2+ channel activity. However, L-selectin-induced adhesion is distinct from that induced by phorbol ester or CD3 crosslinking in being relatively independent of protein kinase C (PKC) activity and actin polymerization. Consistent with the higher levels of L-selectin expression on CD45RA+ (naive) cells, L-selectin crosslinking induces a greater proportion of naive relative to memory cell binding to CAMs and FN. In contrast, exposure to phorbol ester or CD3 crosslinking is more effective in inducing CD45RO+ (memory) cell adhesion. Thus, in addition to its role in leukocyte capture and rolling on the endothelium, L-selectin may contribute to beta 1 and beta 2 integrin-dependent binding and arrest.     

Vancomycin elimination during high-flux hemodialysis: kinetic model and comparison of four membranes

Vancomycin clearance was measured in five patients during dialysis with cuprophane (CU), polysulfone (PS), cellulose triacetate (CT), and polyacrylonitrile (PAN) dialyzers. Vancomycin was significantly cleared during routine high-flux (HF) hemodialysis (HD) with the latter three membranes, but not by CU. Postdialytic rebound of serum vancomycin concentrations was noted following HF dialysis, necessitating use of a two-compartment pharmacokinetic model. Measurement of serum vancomycin concentration immediately postdialysis significantly overestimates intradialytic removal, possibly resulting in inappropriate dose adjustment. Vancomycin infusion during HF HD results in significant drug removal during its administration to the patient, complicating the calculation of an adequate dose.     

Hemodialysis-induced increase in serum lactoferrin and serum eosinophil cationic protein as signs of local neutrophil and eosinophil degranulation

Transient reduction in circulating polymorphonuclear granulocytes and eosinophils were observed early in hemodialysis. About a threefold increase in serum-lactoferrin occurred 2 h from the start of hemodialysis. Increments of the serum levels of eosinophil cationic protein (ECP) were observed as early as 1 h after initiation of hemodialysis, reaching maximum levels (about a fourfold increase from initial levels) 1 h later. When fresh blood was circulated through a dialyzer without having a patient in the circuit considerable increases of lactoferrin and ECP were also found. The intracellular contents of lactoferrin and ECP in granulocytes isolated from peripheral blood were unaffected throughout the dialysis period. Sera obtained at different times during dialysis induced no release of granular proteins from isolated granulocytes in vitro. The raised serum concentrations of lactoferrin and ECP during dialysis suggest that a local degranulation of neutrophils and eosinophils may take place probably in the dialyzer.     

Chemoattractant receptor-induced phosphorylation of L-selectin

The selectin adhesion molecules and chemoattractant receptors synergistically regulate leukocyte migration into lymphoid tissues and sites of inflammation, but little is known about how these families of receptors modulate each other's function. In this study, L-selectin was found to be phosphorylated in lymphoblastoid cell lines, and phosphorylation was enhanced by phorbol ester (phorbol 12-myristate 13-acetate (PMA)) treatment. Interactions between L-selectin and chemoattractant receptors were therefore examined using transfected rat basophilic leukemia cell lines (RBL-2H3) that expressed human L-selectin along with human leukocyte chemoattractant receptors. L-selectin was rapidly phosphorylated in cells treated with chemoattractants, thrombin, IgE receptor agonists, or PMA. Pertussis toxin or the protein kinase C inhibitor, staurosporine, completely blocked chemoattractant receptor-induced phosphorylation of L-selectin. PMA-induced phosphorylation was on serine residues within the cytoplasmic tail of L-selectin that have been well conserved during recent evolution. Although L-selectin phosphorylation was not essential for basal levels of adhesion through L-selectin in transformed cell lines, the rapid increase in ligand binding activity of L-selectin that occurs following leukocyte activation was blocked by staurosporine. These results demonstrate that L-selectin can be phosphorylated following engagement of chemoattractant receptors and suggest that this may be a physiologically relevant mechanism for the synergistic regulation of these receptors during leukocyte migration.     

Soluble L-selectin concentration in bronchoalveolar lavage fluid obtained from infants who develop chronic lung disease of prematurity

AIMS: To explore the changes in neutrophil adhesion molecule expression and release into bronchoalveolar lavage fluid (BAL) obtained from infants who developed chronic lung disease (CLD). METHODS: BAL fluid was obtained from 37 infants: 18 (median gestation 26 weeks, birthweight 835 g) who developed CLD, 12 (29 weeks, 1345 g) with respiratory distress syndrome (RDS) and seven control infants (33 weeks, 2190 g). RESULTS: Soluble L-selectin (sL-selectin) in BAL fluid from the CLD and non-CLD groups was similar immediately after birth, but in infants who subsequently developed CLD, sL-selectin remained persistently increased (at day 7: CLD 42.6 vs RDS 6.0 ng/ml, p < 0.05; CLD vs controls 1.5 ng/ml; p < 0.05). CD11b/CD18 expression on neutrophils obtained by BAL increased with time to reach a maximum at 17 days of age in infants who developed CLD. CONCLUSIONS: These results suggest that leucocyte traffic persists in infants who develop CLD and may have an important part to play in the pathogenesis of CLD.     

Citrate anticoagulation does not correct cuprophane bioincompatibility as evaluated by the expression of leukocyte surface molecules

BACKGROUND: Citrate, used for the anticoagulation of the extracorporeal dialysis circuit, reduces ionized calcium by chelation and has been claimed to attenuate dialyser membrane bioincompatibility. Dialysis with complement-activating cuprophane membranes is associated with leukopenia which has been related to an increase in adhesion molecule expression on the surface of circulating leukocytes. METHODS: The effect of citrate anticoagulation on the expression of CD11b, CD11c and CD45 on the surface of granulocytes and CD14 on monocytes during haemodialysis with cuprophane membranes, was evaluated by flow cytometric analysis. A comparison of standard heparin vs citrate was performed in 14 chronic haemodialysis patients. During citrate anticoagulation a calcium-free dialysate was used and citrate was infused to obtain a concentration of 4.3 mmol/l blood. The unchallenged 'baseline state' expression of the surface molecules and the increase after ex vivo stimulation with phorbol 12-myristate 13-acetate (delta-PMA) or formyl-methionyl-leucyl-phenylalanine (delta-fMLP) was studied. RESULTS: With heparin, as well as with citrate, a sharp fall in granulocyte and monocyte count was observed after 15 min of dialysis, followed by a recovery at the end of the session. The expression of CD11b, CD11c and CD45 on granulocytes increased markedly during cuprophane dialysis with a peak at 15 min; there were no differences in response between heparin and citrate anticoagulation. Delta-PMA and delta-fMLP for CD45, CD11c and CD14 showed a decrease during cuprophane dialysis vs t0; again there were no differences between heparin and citrate. CONCLUSION: We conclude that the use of citrate was not associated with reduced leukocyte activation as measured by the expression of surface molecules during cuprophane dialysis and that no effect on dialysis leukocytopenia could be registered.     

Induction of acute inflammatory lung injury by staphylococcal enterotoxin B

Superantigens stimulate T lymphocytes at high frequency by interacting with appropriate Vbeta segments of the TCR. Challenge of mice with bacterial superantigens such as staphylococcal enterotoxin B (SEB) induces the systemic release of cytokines resulting in septic shock and death of sensitized animals. Analysis of putative pathogenic mechanisms of T cell-dependent septic shock revealed that administration of SEB results in acute inflammatory lung injury characterized by a profound increase in vascular permeability. Injury was associated with marked leukocyte infiltration of the lung and induction of cell adhesion molecules including VCAM-1, ICAM-1, and P-selectin, but not E-selectin. Lung infiltrating leukocytes consisted of granulocytes, mononuclear phagocytes and NK cells with granulocytes representing the major fraction. Consistent with a role of neutrophils as cellular mediators of inflammatory organ injury, we demonstrate activation of circulating granulocytes in mice treated with SEB. When compared with granulocytes of control mice, peripheral blood granulocytes of SEB-treated mice were found to express increased levels of cell surface Mac-1, to down-regulate expression of L-selectin, and to respond with an increased production of toxic oxygen metabolites upon exposure to FMLP. Interestingly, TNF-alpha further enhanced FMLP-induced oxidant production by granulocytes from SEB-treated but not control mice, suggesting that the systemic response to SEB increases granulocyte sensitivity to TNF-alpha-mediated signals. Together, these results suggest that acute inflammatory lung injury may contribute to the pathogenesis of T cell-dependent lethal shock in mice challenged with bacterial superantigens and indicate common pathogenic mechanisms of lung injury induced by a large number of distinct inflammatory stimuli.     

Identification of podocalyxin-like protein as a high endothelial venule ligand for L-selectin: parallels to CD34

The leukocyte adhesion molecule, L-selectin, mediates the recruitment of lymphocytes to secondary lymphoid organs via interactions with specific ligands presented on high endothelial venules (HEV). Although the HEV-derived ligands for L-selectin are still incompletely defined, they share a common sialomucin-like structure which is thought to present clustered oligosaccharides to the lectin domain of L-selectin. Podocalyxin-like protein (PCLP) is a transmembrane sialomucin that is similar in structure to the well-characterized L-selectin ligand CD34. PCLP has been shown previously to be expressed on the foot processes of podocytes in the kidney glomerulus as well as on vascular endothelium at some sites. We have determined that PCLP is present on HEV, where it binds to both recombinant L-selectin and the HEV-specific monoclonal antibody MECA-79. Furthermore, purified HEV-derived PCLP is able to support the tethering and rolling of lymphocytes under physiological flow conditions in vitro. These results suggest a novel function for PCLP as an adhesion molecule and allow the definition of conserved structural features in PCLP and CD34, which may be important for L-selectin ligand function.     

Reduced intracellular oxidative metabolism promotes firm adhesion of human polymorphonuclear leukocytes to vascular endothelium under flow conditions

The interaction of polymorphonuclear leukocytes (PMN) with the vascular endothelium and their subsequent extravasation to the tissues is a key step during different physiological and pathological processes. In certain of these pathologies the oxygen tension becomes very low, leading to reduced cellular oxidative status. To evaluate the effect of lowering the intracellular redox status in the interaction of PMN with the endothelium, exposure to hypoxic conditions as well as treatment with different antioxidant agents was carried out. PMN exposure to hypoxia enhanced beta2 integrin-dependent adhesion to intercellular adhesion molecule-1-coated surfaces, concomitant with a decrease in the intracellular redox status of the cell. As occurs with hypoxia, treatment with antioxidants produced a decrease in the oxidation state of PMN. These agents enhanced adhesion of PMN to human umbilical vein endothelial cells stimulated with tumor necrosis factor-alpha (TNF-alpha), and this effect was also mediated by beta2 integrins LFA-1 and Mac-1. Adhesion studies under defined laminar flow conditions showed that the antioxidant treatment induced an enhanced adhesion mediated by beta2 integrins with a decrease in the fraction of PMN rolling on TNF-alpha-activated endothelial cells. The up-regulated PMN adhesion was correlated to an increase in the expression and activation of integrin Mac-1, without loss of L-selectin surface expression. Altogether, these results demonstrate that a reduction in the intracellular oxidative state produces an enhanced beta2 integrin-dependent adhesion of PMN to stimulated endothelial cells under conditions of flow.     

Ambulatory blood pressure monitoring in dialysis patients and estimation of mean interdialytic blood pressure

To define blood pressure (BP) patterns and control in dialysis patients, 48-hour ambulatory BP monitoring was performed in 36 hemodialysis and 18 peritoneal dialysis patients. Monitoring began during a dialysis session for hemodialysis patients. Data revealed significantly lower diastolic BP (DBP) and lower diastolic load (percentage of diastolic values > 90 mm Hg) in hemodialysis patients compared with peritoneal dialysis patients (80.6 mm Hg v 88.8 mm Hg, respectively, [P < 0.03] and 26% v 45%, respectively [P < 0.03]) for the 48-hour period. When the 2 days were analyzed separately, the difference in diastolic pressures and loads was significant only for the first (dialysis) day. Similarly, trends toward lower systolic BP (SBP) and systolic load in hemodialysis patients existed throughout monitoring and were greater in magnitude during the first day. BP data were fit to a random-coefficient growth curve model to detect periodicity. This sensitive model did not detect diurnal variation of BP in either group. The incidence of hypotension did not differ between the two groups (2.0% v 1.0% of total observations, hemodialysis v peritoneal dialysis). In the hemodialysis group, the proportion of hypotensive observations was significantly greater during the 4 hours postdialysis compared with other periods (5.6% v 1.6%; P < 0.02), a finding that likely reflects the practice of holding antihypertensives until after hemodialysis. However, patient diaries did not reflect hypotensive symptoms during this time. In the hemodialysis group, mean BP and predialysis BP did not correlate with interdialytic sodium load or weight gain. Predialysis and postdialysis BP (recorded by dialysis nurses) correlated significantly with mean BP. Predialysis SBP overestimated mean SBP by an average of 10 mm Hg, while postdialysis SBP underestimated mean SBP by an average of 7 mm Hg. To create formulas to estimate mean SBP and DBP in hemodialysis patients, multiple linear regression was used to model these variables against age, sex, race, and average prehemodialysis/posthemodialysis BP. The model achieved a high degree of fit (r2 = 0.72 for SBP; r2 = 0.65 for DBP), demonstrating that prehemodialysis and posthemodialysis BP can be used to predict mean BP in hemodialysis patients. In summary, our data show the absence of a diurnal variation of BP in dialysis patients and lower BP in hemodialysis patients compared with peritoneal dialysis patients. Among hemodialysis patients, more hypotension occurred after dialysis compared with other periods, and predialysis and postdialysis BP can be used to model mean BP levels.     

The L-selectin adhesion system

L-selectin is a cell surface glycoprotein expressed on most leukocyte subsets that mediates leukocyte interaction with ligands on lymphoid tissue high endothelial venule cells as well as with ligands on activated endothelium at sites of inflammation in nonlymphoid organs. Similar to two other members of the selectin family, L-selectin behaves as a lectin, recognizing carbohydrate ligands in a calcium-dependent fashion. Recent in vivo studies reveal the importance of L-selectin expression in both normal and pathologic conditions.     

Hemocompatible cellulose dialysis membranes modified with phospholipid polymers

Hemocompatibility is one of the most important properties for hemodialysis membranes. For improvement of the hemocompatibility on a cellulose dialysis membrane, modifications with new blood-compatible phospholipid polymers were carried out. These methods included a direct grafting of the phospholipid monomer on the membrane surface, coating the membrane surface with a water-soluble graft copolymer composed of a cellulose backbone and phospholipid polymer as a branch, and covalent bonding with a reactive phospholipid polymer on the membrane surface. These modified membranes could reduce protein adsorption as well as complement activation and platelet adhesion on the surface without any adverse effects on the membrane performance.     

Hydroxamate-based metalloprotease inhibitor blocks shedding of L-selectin adhesion molecule from leukocytes: functional consequences for neutrophil aggregation

L-selectin is an adhesion molecule that mediates the recruitment of neutrophils to inflammatory sites and initiates the migration of lymphocytes into the peripheral lymph nodes. In response to cell activation, L-selectin is shed from the cell surface, and altered levels of functional soluble L-selectin are detected in the plasma of patients suffering from numerous inflammatory diseases as well as AIDS. The mechanism that regulates L-selectin shedding is poorly understood. Here we show that a hydroxamate-based metalloprotease inhibitor, N-(D,L-[2-(hydroxyaminocarbonyl)- methyl]-4-methylpentano)-L-3-(tert-butyl)-alanyl-L-alanine, 2-aminoethyl amide, which blocks leukocyte TNF, TNF receptor, and IL-6 receptor release, also inhibits L-selectin shedding from neutrophils, eosinophils, and lymphocytes. Moreover, we show that such inhibition of L-selectin shedding profoundly affects neutrophil aggregation and permits reaggregation in the presence of a heterologous stimulus.     

Beta2-integrins mediate stable adhesion in collisional interactions between neutrophils and ICAM-1-expressing cells

The aggregation of human neutrophils in suspension has features that are analogous to their attachment to activated endothelium in that both involve selectin and beta2-integrin adhesion receptors. For the collisional interaction that forms neutrophil aggregates in suspension, there is a tethering step in which L-selectin on neutrophils binds PSGL-1. At relatively low shear rates (100-200 s(-1)) firm adhesion is mediated in equal measure by LFA-1 binding to ICAM-3, and Mac-1 binding to an as yet undefined ligand. In this report we used a mouse melanoma cell line expressing an estimated 700,000 ICAM-1 (CD54) to examine the relative roles of LFA-1 and Mac-1 over the kinetics of heterotypic cell adhesion in shear mixed suspensions. Neither heterotypic nor homotypic neutrophil aggregates formed with application of shear alone. However, the rate of aggregation peaked within seconds of chemotactic stimulation. In contrast to homotypic aggregation, neither L-selectin nor its O-glycoprotein ligands on neutrophils contributed to heterotypic adhesion. Adhesion was inhibited in a dose-dependent manner as ICAM-1 was titrated with blocking mAb. A direct interaction between LFA-1 and ICAM-1 was preferred over the first minute of stimulation, whereas at later times adhesion was supported equally by Mac-1. Activation with MnCl2 also favored participation of the constitutively expressed LFA-1. Application of defined shear in a cone and plate viscometer showed that adhesion to the ICAM-1 cells decreased from a maximum level to baseline as shear rate increased up to 400 s(-1) in a manner typical of integrin adhesion alone. In contrast, homotypic aggregation supported by the transition from selectin to integrin binding exhibited an increase in efficiency up to 800 s(-1). The pathophysiological significance of receptor site density and duration of contact in collisional interactions relevant to leukocyte recruitment compared to leukocyte-endothelial cell interactions on surfaces is discussed.