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At least 19 recordsLinked to original sources

PubMed1991

Monoclonal antibodies to the leukocyte membrane CD18 glycoprotein complex and to intercellular adhesion molecule-1 inhibit leukocyte-endothelial adhesion in rabbits.

Increasing evidence indicates that leukocyte-endothelium adhesion is mediated, in part, by the CD11/CD18 family of heterodimeric glycoproteins expressed on the leukocyte plasma membrane and by intercellular adhesion molecule-1 (ICAM-1) which is expressed on endothelial cells. We have used the technique of intravital microscopy to visualize the microcirculation of the rabbit mesentery and to evaluate effects of antibodies against several adhesion glycoproteins on C5a-induced leukocyte adhesion. Addition of zymosan-activated serum (a source of C5a) to the buffer superfusing the mesenteric microvasculature induced rapid adhesion of leukocytes to the endothelium of post-capillary venules. Monoclonal antibodies R15.7 (anti-CD18), R7.1 (anti-CD11a, LFA-1), and R6.5 (anti-ICAM-1), administered intravenously before C5a exposure, strongly inhibited leukocyte adherence while antibody LM2 (anti-CD11b, Mac-1) produced significant, but weaker, inhibition. If these antibodies were administered after C5a-induced adhesion had begun, both R15.7 and R7.1 displaced adherent leukocytes and prevented further leukocyte accumulation: LM2 and R6.5 did not displace adherent leukocytes or inhibit incoming leukocytes from adhering. These data confirm earlier findings establishing a role for CD18 in leukocyte adhesion in vivo and extend those observations to implicate both CD11a and CD11b in that adhesion. In addition, we report that ICAM-1 mediates, in part, the initial leukocyte-endothelial cell adhesion following C5a exposure in vivo.

Animals↗

PubMedDate not supplied

Ultrastructural damage of leukocytes procured by the Leukopak: vulnerability of leukocytes to mechanical injury.

Because of the often observed undesired effects in patients transfused with leukocytes collected by continuous filtration leukapheresis (CFL), we have investigated the morphology of these cells in the hope that such studies may help evaluate their in vivo functions. Aliquots of CFL samples, procured by the Fenwal Leukopak and taken before and after tapping the filters, were examined. Leukocytes prepared by dextran sedimentation served as controls and were used to demonstrate the vulnerability of these cells to mechanical injury. The morphology of leukocytes harvested by filtration leukapheresis was markedly altered, ranging from formation of cytoplasmic projections and vacuoles to disintegration of entire cells. The severe changes were only observed in samples collected after the filters were tapped. The number of cells involved varied from donor to donor. In some cases more than half of the examined leukocytes showed signs of damage. Dextran sedimentation leukocytes retained their normal ultrastructure. However, substantial injuries were inflicted on dextran sedimentation collected leukocytes following brief periods of vortexing. Our results indicate that leukocytes are quite vulnerable to mechanical injury, and the major cause of damage found in Leukopak-isolated leukocytes is the tapping of the filters. The toxic reactions in some recipients transfused with Leukopak-collected leukocyte preparations may result from materials released from disrupted leukocytes. We believe that the employment of the continuous filtration to procure leukocytes with the present procedure should be reviewed.

Blood Transfusion, Autologous↗

PubMed1975

An evaluation of the role of leukocytes in the pathogenesis of experimentally induced corneal vascularization. II. Studies on the effect of leukocytic elimination on corneal vascularization.

Investigations on several experimental models in the past have supported the hypotheses that corneal vascularization is a manifestation of the inflammatory response and that leukocytes perform an essential role in stimulating corneal vascular ingrowth. To evaluate the possible role of leukocytes further in this phenomenon, the effect of leukocyte elimination on corneal vascularization induced by silver nitrate cauterization was investigated. Weanling Fischer albino rats received doses of total body x-irradiation ranging from 1100 to 2100 rads to deplete circulating leukocytes, and corneal silver nitrate cauterization was performed 4 days later. In this model, animals that received 1500 rads or more total body x-irradiation became severely leukopenic within 4 days. As a rule, neither leukocytes nor blood vessels invaded the cauterized corneas, whereas both a leukocytic and vascular invasion occurred at lower doses of irradiation that did not totally eliminate circulating leukocytes. Corneal vascularization ensued if the corneal cauterization was performed immediately after total body x-irradiation with 1500 rads before the leukopenic effect of x-irradiation occurred. Control studies in which the cornea was cauterized 4 days after only the head received 1500 rads x-irradiation ruled out the possibility of irradiation-induced limbal endothelial damage as the explanation for the vascular suppression observed by x-ray treatment. In nonirradiated rats, silver nitrate cauterization of the cornea consistently induced corneal vascularization by 2 to 3 days. In further experiments, methylprednisolone acetate was administered subconjunctivally after corneal cauterization. This corticosteroid inhibited the infiltration of leukocytes and the subsequent vascular invasion into the corneal stroma, if administered immediately after silver nitrate cauterization. However, when the same glucocorticoid was administered 1 day after cauterization, both a leukocytic infiltration and vascular ingrowth occurred but to a less severe degree than in non-glucocorticoid-treated cauterized corneas. These investigations together demonstrated that a vascular ingrowth of the cornea did not follow corneal cauterization with silver nitrate in the absence of leukocytes, and gives further support to the hypothesis that leukocytes serve a crucial function in corneal vascularization.

Animals↗

PubMed1976

Separation of mononuclear leukocytes and polymorphonuclear leukocytes from equine blood.

The present study describes a two step technique for the separation of mononuclear leukocytes or mononuclear and polymorphonuclear leukocytes from whole equine blood. First, the leukocyte rich plasma was obtained by sedimentation of erythrocytes in the undiluted blood. Subsequently, separation of the different populations of white blood cells was performed by centrifugation with different gradients overlaid with the leukocyte rich plasma. The optimal separation of the mononuclear cells was obtained by the centrifugation of the leukocyte rich plasma overlaying the gradient containing 24 parts of 9.5% ficoll and ten parts of 34% isopaque. The mononuclear leukocytes (95% lymphocytes and 5% monocytes) formed a monolayer band at the plasma-ficoll-isopaque interface and other blood cells migrated to the bottom of the tube. For the separation of mononuclear and granular leukocytes from the blood, the gradient containing 24 parts of 10% ficoll and ten parts of 34% isopaque was used. The separated monuclear leukocytes responded to stimulation with phytohemagglutin and viability of both mononuclear and polymorphonuclear leukocytes was not affected by ficoll-isopaque separation.

Animals↗

PubMed1992

Effects of hydrodynamics and leukocyte-endothelium specificity on leukocyte-endothelium interactions.

In vivo microscopy was used to assess the relative contribution of hydrodynamic forces (network topography and shear rate) and the specificity for leukocytes to interact with venular endothelium as determinants of leukocyte-endothelium interactions. To ascertain this, microvascular networks in the rat and rabbit mesentery were examined under normograde and mechanically induced retrograde flows to determine the effect of reversed flow on leukocyte-endothelium interactions in arterioles and venules. The data indicate that retrograde perfusion under hemodynamic (red blood cell velocity and shear rate) states equivalent to normograde flow significantly increased leukocyte marginating flux in arterioles (from 0 to 0.5 cells/5 sec) and decreased flux significantly in venules (from 1.0 to 0.2 cells/5 sec). The increased flux in arterioles under retrograde conditions, however, was significantly lower than the flux in venules under normograde conditions and the decreased flux in venules during retrograde flow was significantly greater than the flux in arterioles during normograde flow. This apparent discrepancy appears to be the result of a heterogeneous distribution of adhesive receptors on vascular endothelium. Furthermore, marginating leukocytes in arterioles made only brief contact with the endothelium before being swept away while marginating leukocytes in venules during normal and retrograde perfusion rolled along the vascular wall, with similar velocities in both directions. In conclusion, although hydrodynamic forces are important in facilitating leukocyte margination through mechanisms of radial migration, it is leukocyte-endothelium specificity in venules that ultimately determines leukocyte-endothelium interactions.

Animals↗

PubMed1975

Determination of the glycogen content in single neutrophil leukocytes using a micromodel of leukocyte glycogen.

The kinetics of the periodic acid oxidation as part of the periodic acid-Schiff reaction was studied by combined microinterferometry and microspectrophotometry in micromodel systems of liver glycogen and leukocyte glycogen as well as in neutrophil leukocytes. The initial formation of Schiff-positive chromogens was more rapid in neutrophil leukocytes than in liver or leukocyte glycogen. The chromogen formation was, however, practically complete within 60 min in both neutrophil leukocytes and leukocyte glycogen, but this did not appear to be the case in liver glycogen. Differences in the rate of chromogen formation may depend on various factors such as differences in the source and treatment of the glycogen. The complete periodic acid-Schiff reaction appears to be a measure of the glycogen amount in neutrophil leukocytes and the microdroplet system of leukocyte glycogen is considered to be an appropriate model for the estimation of the glycogen amount in single neutrophil leukocytes. A mean value of 13.3 10-12 g glycogen per normal human neutrophil was found.

Glycogen↗

PubMed1991

Flavone acetic acid directly induces expression of cytokine genes in mouse splenic leukocytes but not in human peripheral blood leukocytes.

Flavone-8-acetic acid (FAA) is a flavonoid drug that augments mouse natural killer activity, induces cytokine gene expression, and synergizes with recombinant interleukin 2 for the treatment of murine renal cancer. However, FAA has been largely inactive in human clinical trials. In the present study we investigated the ability of FAA treatment to directly induce cytokine mRNA expression in total mouse splenic leukocytes and selected leukocyte subsets, as well as in total human peripheral blood leukocytes. Analysis of RNA isolated from FAA-treated mouse splenic leukocytes demonstrated that treatment with greater than or equal to 100 micrograms/ml of FAA induced expression of tumor necrosis factor alpha (TNF-alpha) mRNA by 1 h and induced maximal expression of TNF-alpha, alpha-interferon, and gamma-interferon mRNA within 3 h. The expression of all cytokine genes was diminished by 6 h. Interferon biological activity was detected in the supernatants of mouse splenic or peripheral blood leukocytes after treatment with FAA. These results correlate well with the previously reported induction of cytokine mRNA genes and biological activity by FAA in vivo. In contrast, FAA did not induce detectable mRNA expression or cytokine protein secretion by human peripheral blood leukocytes under similar conditions. These results demonstrate that FAA can directly stimulate cytokine gene expression in mouse but not in human leukocytes. Further studies performed with highly purified positively selected mouse CD4+ or CD8+ splenic T-lymphocytes, as well as purified B-cells, demonstrated that the FAA-induced expression of gamma-interferon mRNA was mainly induced in the CD8+ lymphocyte subset. alpha-Interferon mRNA was expressed largely in the B-cell population, while TNF-alpha mRNA was induced in all leukocyte subsets tested. Therefore, these results suggest that the immunomodulatory effects of FAA in mice are direct, but different cytokines are induced from different leukocyte subsets. Further, the data suggest that flavonoid compounds or analogues that stimulate cytokine gene expression in human cells might be therapeutically active in cancer patients.

Animals↗

PubMed1978

Amplification of the activity of human leukocyte inhibitory factor (LIF) by the generation of a low molecular weight inhibitor of PMN leukocyte chemotaxis.

Leukocyte inhibitory factor (LIF), which was derived from human peripheral blood lymphocytes by stimulation with concanavalin A ad partially purified by Sephadex G-100 gel filtration, inhibited the in vitro spontaneous migration and chemotaxis of human PMN leukocytes as assessed in a Boyden chamber micropore filter assay. The inhibitory activity was attributed to LIF, a principle defined in terms of its inhibition of PMN leukocyte migration from glass capillary tubes since it was preferentially directed to PMN leukocytes as compared to mononuclear leukocytes, exhibited a size comparable to LIF by gel filtration, and was inactivated by diisopropyl fluorophosphate in parallel with LIF. Incubation of PMN leukocytes with LIF released additional inhibitory activity, distinct from LIF, which resembled the neutrophil-immobilizing factor (NIF) by virtue of its approximate m.w. of 4000 by filtration on Sephadex G-25, inactivation by trypsin digestion, and preferential noncytotoxic inhibition of spontaneous migration and chemotaxis of PMN leukocytes as compared to mononuclear leukocytes. Thus LIF inhibits PMN leukocyte migration both by a direct action on the cells and by an amplification pathway that is mediated by low m.w. chemotactic inhibitors similar to NIF.

Chemotaxis, Leukocyte↗

PubMed1992

Chemoattractant-induced firm adhesion of leukocytes to vascular endothelium in vivo is critically dependent on initial leukocyte rolling.

Leukocyte rolling and firm adhesion at the venular endothelium are two discrete events in the cellular inflammatory response mediated via selectin and integrin adhesion molecules, respectively. The dependency of chemoattractant-induced firm leukocyte adhesion on the preceding rolling interaction was investigated in rat mesenteric microvessels through use of intravital microscopy. Leukocyte rolling was dose-dependently inhibited by systemic treatment with the sulphated polysaccharide fucoidin. The firm leukocyte adhesion following stimulation with the chemotactic peptide fMLP was similarly inhibited when fMLP challenge was performed subsequent to inhibition of leukocyte rolling by fucoidin. Thus, based on paired observations in single venules before and after fucoidin treatment, reduced rolling leukocyte flux prior to fMLP challenge was paralleled over a wide range by a proportional decrease in fMLP-induced leukocyte adhesion. The results demonstrate quantitatively a close relationship between the extent of leukocyte rolling and the magnitude of the subsequent firm adhesion response, and, that an initial rolling interaction is a precondition for firm adhesion to occur at physiological blood flow rates in vivo.

Animals↗

PubMed1976

An evaluation of the role of leukocytes in the pathogenesis of experimentally induced corneal vascularization. III. Studies related to the vasoproliferative capability of polymorphonuclear leukocytes and lymphocytes.

Studies in the past have suggested that leukocytes are a prerequisite to corneal vascularization. To test this hypothesis further, experiments were conducted to determine whether the intracorneal instillation of polymorphonuclear leukocytes, lymphocytes, or components of leukocytes would induce a corneal vascular ingrowth. These cells or cellular fractions were injected intracorneally into Fisher albino rats whose circulating leukocytes had been depleted by total body x-irradiation. Polymorphonuclear leukocytes isolated from glycogen-induced peritoneal exudates caused a corneal vascular invasion, but lymphocytes obtained from thymus, spleen, and lymph nodes failed to do so. To learn whether an extractable factor could be isolated from polymorphonuclear leukocytes these cells were suspended in isotonic saline, ultrasonified and then centrifuged at 101,952g for 1 hour. Aliquots of the resulting sediment and supernatant were injected intracorneally into rats with radiation-induced leukopenia. The nonsedimentable supernatant caused corneal vascularization, but the sediment did not provoke the phenomenon. These studies not only provide further support for the hypothesis that leukocytes initiate corneal vascularization, possibly by the release of one or more heat labile chemical mediators, but directly implicate the polymorphonuclear leukocyte in this process.

Animals↗

PubMed1991

Proteolysis of gelatin-bound fibronectin by activated leukocytes: a role for leukocyte elastase.

Fragmentation of subendothelial matrix-bound fibronectin by proteases released from stimulated leukocytes has been implicated in lung vascular injury. We studied the degradation of fibronectin bound to denatured collagen by inflammatory polymorphonuclear leukocytes (PMNL). Tissue culture wells coated with denatured collagen (gelatin) were pretreated with 125I rat plasma fibronectin to allow for fibronectin binding prior to the addition of rat inflammatory PMNL. The release of both intact and fragmented fibronectin from the 125I-labelled artificial matrix was quantified following the addition of PMNL stimulated by the phagocytosis of opsonized zymosan as well as leukocyte elastase. Stimulated PMNL released three times more radiolabelled fibronectin from the denatured collagen surface during a 4 h incubation as compared with unstimulated PMNL. This pattern of 125I-fibronectin release could also be elicited by the addition of purified leukocyte elastase alone, in the absence of PMNL. The release of radiolabelled fibronectin by stimulated PMNL was blocked in a dose-dependent manner by the addition of both methoxysuccinyl-alanine-alanine-valine chloromethyl ketone (AAPVCK), a leukocyte elastase specific inhibitor as well as phenylmethylsulfonylfluoride (PMSF), a non-specific serine protease inhibitor. Western blot analysis coupled with autoradiography confirmed the presence of fibronectin fragments in the medium after addition of PMNL or leukocyte elastase. The large molecular weight fragments (60-200 kD) were not labelled, but the smaller molecular weight fragments (less than 45 kD), derived from the artificial matrix, were labelled. Thus, fibronectin complexed with denatured collagen is susceptible to proteolytic degradation by stimulated inflammatory PMNL. Such a process may have a role in the pathogenesis of acute vascular injury following microvascular margination of activated blood leukocytes.

Amino Acid Chloromethyl Ketones↗

PubMed1991

Positive immunoselection--a method of isolating leukocytes from leukocytic reacted human cervical mucus samples.

In this brief communication we report a simple and accurate method of isolating and quantifying specific leukocytes from midcycle human cervical mucus, using monoclonal antibody-coated magnetic beads. Cervical mucus samples (pre- and postinsemination) were broken down enzymatically and incubated with a series of these beads. This method of positive immunoselection consistently retrieved representative levels of leukocytes (means = 73.8% +/- 1.59%; mean leukocyte retrieval rate +/- S.E.) from the cervical mucus samples. Significantly more leukocytes (P less than 0.0001) were isolated from the postinsemination samples, the predominant leukocyte of which was the neutrophil, which comprised 83% of the leukocyte population. These results reaffirm that a leukocytic influx is initiated across the human uterine cervix following the introduction of semen samples, the function of which is possibly phagocytic clearance of the nonfertilizing population of sperm.

Antibodies, Monoclonal↗

PubMed1991

Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and the leukocyte beta 2 integrins in vivo.

The lectin homing receptor LECAM-1 (LAM-1, Leu8) and the beta 2 integrins, particularly Mac-1 (CD11b/CD18), participate in leukocyte-endothelial cell interactions in inflammation. LECAM-1 is rapidly shed while Mac-1 expression is dramatically increased upon neutrophil activation, suggesting functionally distinct roles for these molecules. Using intravital video microscopy, we have compared the effect of antibodies against LECAM-1 and CD18 on leukocyte interactions with rabbit mesenteric venules. Anti-LECAM-1 monoclonal antibody and its Fab fragments inhibited initial reversible leukocyte rolling along the vascular wall. Anti-CD18 monoclonal antibody had no effect on rolling but prevented subsequent firm attachment of leukocytes to venular endothelium. These results support a two-step model of leukocyte-endothelial cell interactions: reversible rolling mediated in part by LECAM-1 facilitates leukocyte recruitment by the local microenvironment and precedes activation-dependent firm attachment involving beta 2 integrins.

Animals↗

PubMed1979

Digestion of the fifth component of complement by leukocyte enzymes. Sequential generation of chemotactic activities for leukocytes and for tumor cells.

Leukocytes contain within their lysosomal granules enzymatic activity that will generate from C5 chemotactic activity for leukocytes (neutrophils) and tumor (Walker carcinosarcoma) cells. Similar activity has been found in phagocytic supernatant fluids from neutrophils and in purified preparations of the leukocyte neutral proteases elastase and cathepsin G. White leukotactic activities can be generated from either the third (C3) or the fifth (C5) components of complement, only C5 serves as a source for generation of the chemotactic activity for tumor cells. As has been previously shown with trypsin, the C5-related chemotactic activities generated by leukocyte proteases are time-dependent: leukotactic activity appears early, then disappears, and is replaced by chemotactic activity for tumor cells. The generation of these chemotactic activities from C5 is blocked by prior treatment of leukocyte preparations with the neutral protease inhibitor Trasylol. The demonstration that enzyme activities from leukocytes have the ability to generate tumor cell chemotactic factors from C5 suggests a possible mechanism by which the development of metastatic lesions may be promoted at sites of tissue injury or inflammation.

Animals↗

PubMed1975

The effect of leukocyte hydrolases on bacteria. III. Bacteriolysis induced by extracts of different leukocyte populations and the inhibition of lysis by macromolecular substances.

The lysis of 14C-labeled bacteria by hydrolases of human and rabbit leukocytes was studied in vitro. While Staphylococcus albus, Streptococcus faecalis, and Streptococcus mutans were highly susceptible to lysis, Staphylococcus auresus was intermediate in its susecptibility to lysis by the leukocyte enzymes. Group A Streptococcus, Listeria monocytogenes, Shigella flexneri, Escherichia coli, and Mycobacterium smegmatis were very resistant to degradation by these enzymes. The lytic activity of leukocyte lysates from human and rabbit blood was probably due to acid hydrolases of polymorphonuclear leukocytes. Extracts of human blood monocytes and of rabbit peritoneal and lung macrophages were less lytic for the bacteria tested. Lymphocytes and platelet extracts were not bacteriolytic. The lytic effect of the leukocyte lysates was not inhibited by KCN or sodium azide, but was abolished to a large extent by cationic polyelectrolytes such as protamine sulfate, histone and leukocyte cationic proteins, and poly-lysine, as well as by the anionic polyelectrolytes such as heparin, chondroitin sulfate, DNA, carrageenin, alginate sulfate, dextran sulfate, and ploy-L-glutamic acid. Other potent inhibitors of bacteriolysis were trypan blue, congo red, phosphatidic acid, normal immunoglobulins, and components of streptococcal cell wall.

Animals↗

PubMed1978

Neutralizing antibodies against human leukocyte, lymphoblastoid and fibroblast interferons elicited by immunization with human leukocyte interferon.

Guinea pigs, rabbits, and sheep were immunized with partially purified human leukocyte interferon. The antisera were tested for their neutralizing activities against human leukocyte, lymphoblastoid (Namalva) and fibroblast interferons. Rabbits and sheep developed high levels of neutralizing antibodies against all three interferons. The ratios of the neutralizing activities of leukocyte/lymphoblastoid interferons varied from 1 to 25 and those of leukocyte/fibroblast interferons from 2 to 500. The ratios increased with prolonged immunization. The guinea pigs developed relatively low levels of anti-leukocyte and anti-lymphoblastoid antibodies and as a rule failed to produce detectable neutralizing activity against fibroblast interferon. One sheep was given a booster injection of fibroblast interferon after preimmunization with leukocyte interferon. The booster injection stimulated a rise in antibody levels, not only for fibroblast interferon, but also for leukocyte and lymphoblastoid interferons. The antigenic relationships between leukocyte, lymphoblastoid and fibroblast interferons are discussed.

Animals↗

PubMed1976

Decreased ability of blood leukocytes from patients with tumors of the urinary bladder to act as stimulator cells in mixed leukocyte culture.

Blood leukocytes from patients with active neoplasms of the urinary bladder were found to have a decreased ability to stimulate in one-way mixed leukocyte culture (MLC). The ability of the patients' leukocytes to act as stimulator cells in one-way MLC was assessed by simultaneous comparison to the ability of leukocytes from normal individuals to stimulate. In addition, the ability of the patients' leukocytes to act as responder cells in the one-way MLC was evaluated. Cells from 31 (56%) of 55 patients with active disease exhibited subnormal stimulatory activity in the MLC while 26 of these 31 patients (84%) had normal responsiveness. Cells from 9 of the 55 failed to respond normally. Poor stimulation occurred with both early and advanced disease, and the stimulatory activity increased after tumor removal in 12 of 15 patients who had previously shown subnormal stimulation. Six patients without active disease at the time of testing, in addition to the 55, exhibited normal levels of stimulation and responsiveness. This defective stimulatory activity is suggestive of an acquired, disease-related phenomenon and is not necessarily associated with decreased blood leukocyte responsiveness.

Adult↗

PubMed1991

Function and evolutionary conservation of distinct epitopes on the leukocyte adhesion molecule-1 (TQ-1, Leu-8) that regulate leukocyte migration.

The leukocyte adhesion molecule-1 (LAM-1, TQ=1, Leu-8) in humans, like its murine homologue, MEL-14, is the principal receptor that mediates the binding of leukocytes to high endothelial venules (HEV) of peripheral lymph nodes. In this study, several regions of the protein which mediate receptor function were identified by using a large panel of murine mAb reactive with LAM-1. Individual mAb reacted with LAM-1+ cells with characteristic intensities of immunofluorescence staining, and each bound both lymphocytes and neutrophils. Lymphocyte attachment to HEV was significantly inhibited by the binding of five mAb. In contrast, only two of these mAb were able to completely block the binding of phosphomannan monoester core complex from the yeast Hansenula holstii cell wall (PPME), a phosphomannan monoester core polysaccharide that serves as a soluble model of the natural ligand of LAM-1. Interestingly, the binding of two anti-LAM-1 mAb to cells induced a significant increase in PPME binding, reminiscent of the increase in receptor affinity observed after leukocyte activation. Antibody cross-blocking studies indicated that many of the functionally important epitopes were spatially distinct, and domain mapping indicated that they recognized distinct domains of LAM-1. The expression and function of these epitopes were further assessed by using a variety of animal species to further characterize the functionally relevant epitopes defined in these studies. At least some anti-LAM-1 mAb reacted with leukocytes from monkey, cow, rabbit, sheep, dog, cat, pig, and goat, but not from chicken, rat, or mouse. The reactivity of anti-LAM-1 mAb in several animal species correlated with the ability of leukocytes to bind PPME, and mAb that inhibited lymphocyte binding to HEV in man could also inhibit this function in rhesus monkey and dog. Thus, several LAM-1 epitopes are structurally and functionally well conserved throughout recent mammalian evolution, emphasizing an important role for LAM-1 in the regulation of leukocyte traffic.

Animals↗