Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Integrin alpha4beta1”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,135 records · Page 63Linked to original sources
PubMed2003

[Serum concentration of soluble vascular-cellular adhesion molecule-1 (VCAM-1) and expression of its receptor VLA-4 on the surface of peripheral blood and decidual lymphocytes of preeclamptic women].

INTRODUCTION: Vascular-cellular adhesion molecule-1 (VCAM-1) overexpression on the cells' surface is stimulated by pro-inflammatory cytokines, bacterial endotoxins, reactive oxygen species and lipid peroxides. In the serum also the soluble form of VCAM-1 (sVCAM-1) is present. The beta 1-integrin family molecule VLA-4 (CD49d) is natural ligand for VCAM-1. Increased concentrations of sVCAM-1 as well as overexpression of VLA-4 were observed during inflammatory reaction. THE AIM: To study sVCAM-1 serum concentrations and CD49d+ subpopulations of peripheral blood and decidual lymphocytes of the 3rd trimester healthy and preeclamptic women. MATERIALS AND METHODS: The study groups: n = 21 healthy pregnant women, n = 33 preeclamptic women (preeclampsia defined as blood pressure > 140/90 mmHg with proteinuria > 0.3 g/24 h). Clinical states of known pathogenesis which could possibly interfere with values of studied parameters were excluded. Exclusion criteria were also uterine contractions and premature rupture of amniotic membranes. Decidua was collected exclusively during elective caesarean sections. The sVCAM-1 concentration (ng/ml) was estimated using ELISA procedure, while percentage (%) of CD49d+ lymphocytes in the whole blood and homogenized decidual tissue, using flow cytometry. The results were presented as median value with 25% and 75% cut off values. Statistical analysis was performed with U-Mann-Whitney test (p < 0.05). RESULTS: Preeclamptic women presented with increased sVCAM-1 serum concentrations (532.5 (400.0/605.0) ng/ml vs. 387.0 (320.0/416.5) ng/ml, p < 0.0005), increased (%) of CD49d+ peripheral blood (92.0 (88.0/96.0)% vs. 52.9 (47.5/55.8)%, p < 0.0000001) and CD49d+ decidual lymphocytes (88.0 (84.0/90.0)% vs. 80.5 (74.0/85.6)%, p < 0.05). CONCLUSION: Described change suggest that immunological mechanisms similar to inflammatory reaction could be involved in pathogenesis of preeclampsia in peripheral blood as well as locally inside maternal-fetal interface.

Adult↗
PubMed2003

[Effect of matrix composition on chemotaxis response of monocytes stimulated by monocyte chemoattractant protein-1].

MCP-1-stimulated chemotaxic response of monocytic cell line THP-1 and peripheral blood monocytes were investigated through extra cellular matrix proteins fibronectin, fibrinogen and fibrinogen degradation products. Cellular migration was significantly decreased in the presence of fibrinogen as compared with fibronectin. Fibrinogen proteolysis with plasmin generating D and E degradation products, resulted in increase of the chemotaxic response.

Cell Line↗
PubMed2004

Quantitative expression of the major homing integrins alphaL and alpha4 on human cord blood hematopoietic progenitor and stem cells.

An increased traffic of hematopoietic progenitor cells (HPC) between bone marrow and peripheral organs is a peculiar feature of the allergic inflammation. It has been recently reported that the sublingual form of specific immunotherapy (SLIT) is capable of reducing such an increased HPC traffic. The House Dust Mite major antigen Der p1 has been proved to up-regulate the expression of the ICAM-1 and VCAM-1 endothelial addressins, supporting the view of an inflammatory cell recruiting at the site of allergen extract administration. In the present work we have investigated, by flow-cytometric techniques, the expression of the two major integrins CD11a (LFA-1) and CD49d (VLA-4) that are the homing receptor cognate for ICAM-1 and VCAM-1 on human cord blood CD34 hematopoietic progenitor and stem cells. Even if both the investigated molecules resulted detectable on CD34+ HPC surfaces, being the system redundant, the density of the cellular expression was significantly higher for CD49d (median value: 158) than CD11a (median value: 20.5), suggesting a preferential usage of the homing axis VLA-4/VCAM-1. Results consistency with outcomes of clinical trials that relate SLIT efficacy to allergen dosage is discussed.

Antigens, CD34↗
PubMed1997

[Study on the relationship between the expression of adhesion molecules and the invasiveness of acute myeloid leukemia cells].

OBJECTIVE: To study the relationship between the expression of adhesion molecules CD49d (VLA-4) and CD11a (LFA-1) and the invasiveness of acute myeloid leukemia (AML) cells. METHODS: Peripheral blood and/or bone marrow samples from 50 AML patients were investigated by APAAP and Western blotting method. RESULTS: Extramedullary invasion developed in 32 of 50 patients (64%). The expression of CD49d and CD11a in the invasive group was much higher than that in the non-invasive group (P<0.005), while the difference between the leukemic cells from bone marrow and peripheral blood for CD49d/CD11a expression was not significant. CONCLUSION: AML cells might adhere to and get through vascular endothelium by CD49d/VCAM-1 and CD11a/ICAM-1 adhesion mechanism, and the expressions of CD49d and CD11a were not critically responsible for the release of leukemic cells from bone marrow.

Adolescent↗
PubMed2004

Assessment of selected adhesion molecules and lymphocyte subpopulations in children with IgA nephropathy.

PURPOSE: The aim of the study was to assess the expression of selected adhesion molecules on mononuclear cells of peripheral blood and lymphocyte subpopulations in children with IgA nephropathy (IgAN). MATERIAL AND METHODS: 14 children with IgAN and 20 healthy controls were included in the study. Flow cytometry was used to determine the expression of such adhesion molecules as L selectin (CD62L), VLA-4 integrin (CD49d), intracellular molecule ICAM-1 (CD54) and cytotoxic lymphocyte molecule CTLA-4 (CD152), as well as the lymphocyte antigens: CD3, CD4, CD8, CD19, CD1656 (NK), CD4 and CD8 RO+ and RA+. RESULTS: The findings revealed that the expression of the adhesion molecules VLA-4 and CTLA-4 did not differ from that of the healthy controls (p > 0.05). However, the expression of CD62L (L-selectin) was increased (p < 0.05). The expression of ICAM-1 was reduced, but not significantly, compared to the control group (p > 0.05). We found a decrease in the expression of NK cells (CD1656) and CD4/CD8 ratio, and an increase in CD8 cells (p < 0.05). In the group of 9/14 children, with proteinuria over 1.0 g/24 hours, a decreased expression of CD4 was additionally found (p < 0.05). CONCLUSIONS: The children with IgAN show: 1. Changes in peripheral lymphocyte subpopulations involving an increase in CD8 cells and a decrease in CD1656(NK) cells, a reduction in the CD4/CD8 ratio, and additionally in cases with proteinuria a reduction in CD4 cell count, 2. Increased expression of L-selectin (CD62L) on peripheral blood mononuclear cells.

Adolescent↗
PubMed2005

[Effects of ligustrazine on expression of VCAM-1/VLA-4 in syngenic bone marrow transplantation of mice].

To explore the effect of ligustrazine on the expression of adherent molecule VCAM-1/VLA-4 of bone marrow cells in syngenic bone marrow transplantation (BMT) mice, the mice were divided into 3 groups: normal group (which received no treatment), BMT control group and ligustrazine-treated groups. BMT mouse models were established. The BMT control group and the ligustrazine-treated group were orally administered 0.2 ml saline per mouse and 2 mg ligustrazine per mouse, respectively, twice a day. On the day 7, 14, 21, 28 after BMT, mice were respectively killed. Bone marrow nucleated cells were detected, and then the expression of VCAM-1/VLA-4 was assayed by immunohistochemistry, RT-PCR and flow cytometry analysis, respectively. The results showed that in ligustrazine-treated group, the accounts of bone marrow nucleated cells on the day 7, 14, 21, 28 after BMT were all higher than that in BMT control group. The expression level in the ligustrazine-treated group was significantly higher than that in the BMT control group (P < 0.05 or P < 0.01). It is concluded that ligustrazine can enhance VCAM-1/VLA-4 expression in bone marrow after syngenic bone marrow transplantation in mice, which may be related to the mechanisms underlying the ligustrazine accelerating hematopoietic reconstitution in allogenic bone marrow transplantation.

Animals↗
PubMed2005

Modulation of homing properties of primitive progenitor cells generated by ex vivo expansion.

BACKGROUND AND OBJECTIVES: The maintenance of adequate interactions with the bone marrow (BM) microenvironment is critical to ensure efficient homing of ex vivo-expanded hematopoietic cells. This study was intended to assess adhesion and migration properties of long-term culture-initiating cells (LTC-IC) harvested after self-renewal division in ex vivo culture and to determine their susceptibility to growth-inhibitory signals mediated by adhesion to BM stromal ligands. DESIGN AND METHODS: We used cell tracking to isolate primitive LTC-IC that had accomplished 1 or 2 divisions ex vivo. Adhesion, migration and growth inhibition of divided LTC-IC were determined in the presence of purified BM ligands, and compared to the properties of uncultured LTC-IC. RESULTS: As compared to undivided LTC-IC, adhesion and migration mediated by very late antigen (VLA)-4 integrin across both vascular cell adhesion molecule-1 (VCAM-1) and fibronectin (Fn) were downregulated in post-mitotic LTC-IC. Conversely, binding and motility via VLA-5 across Fn were stimulated. No changes occurred in LTC-IC interactions with intercellular adhesion molecule-1 (ICAM-1) or with E- or P-selectin. Proliferation of uncultured LTC-IC was inhibited by VLA-4-mediated binding to VCAM-1 and the CS-1 domain of Fn, as well as binding to P-selectin. Growth of ex vivo-generated LTC-IC became unresponsive to these 3 ligands but was suppressed through VLA-5 engagement by the cell binding domain of Fn. INTERPRETATION AND CONCLUSIONS: The generation of LTC-IC in expansion culture is associated with functional alterations of adhesion receptors, modulating not only binding and migration in the BM but also responsiveness to adhesion-mediated growth inhibitory signals. Such changes may limit homing and engraftment of expanded primitive stem/progenitor cells.

AC133 Antigen↗
PubMed2006

Role of VLA-4 in the development of allergic conjunctivitis in mice.

PURPOSE: The severity of allergic conjunctivitis (AC) correlates with the degree of eosinophil infiltration into the conjunctiva, which is believed to be mediated by chemokines and adhesion molecules. The adhesion molecule very late antigen (VLA)-4 and its ligand, vascular cell adhesion molecule (VCAM)-1, are known to play important roles in eosinophil infiltration. However, the expression and function of VLA-4 in AC have not been investigated in detail. We sought to characterize VLA-4-expressing cells in the conjunctivas of mice that are developing experimental AC (EC) and to determine whether the interaction between VLA-4 and VCAM-1 is needed for the infiltration of eosinophils into the conjunctiva in AC. METHODS: EC was induced in Balb/c mice by active immunization with ragweed (RW) or adoptive transfer of RW-primed splenocytes, followed by RW challenge. Twenty-four hours after RW challenge, the conjunctivas were harvested. The conjunctivas from naive mice or mice developing EC were evaluated for VLA-4 and VCAM-1 expression by immunohistochemistry and immunofluorescent analyses. To investigate whether the interaction between VLA-4 and VCAM-1 is needed for the genesis of AC, mice developing EC were treated with anti-VLA-4 or anti-VCAM-1 antibodies two h before and after RW challenge. As a control, EC-developing mice were treated with normal rat IgG. Twenty-four hours after RW challenge, the conjunctivas were harvested for histological analysis. RESULTS: Upon induction of EC, VLA-4-expressing cells infiltrated the conjunctiva but the constitutive VCAM-1 expression around conjunctival vessels was not augmented. Immunofluorescent analyses demonstrated that most of the T cells infiltrating the conjunctiva expressed VLA-4 but only half of the infiltrating eosinophils expressed it. Treatment with both anti-VLA-4 and anti-VCAM-1 antibodies significantly suppressed the infiltration of eosinophils into the conjunctiva that was induced by either active immunization or splenocyte transfer. CONCLUSIONS: These results confirm that VLA-4-expressing cells infiltrate the conjunctiva and that the interaction between VLA-4 and VCAM-1 is needed for the development of EC.

Adoptive Transfer↗
PubMed2006

LFA-1 and VLA-4 involved in human high proliferative potential-endothelial progenitor cells homing to ischemic tissue.

Cumulative evidences have revealed that endothelial progenitor cell (EPC) transplantation can promote the neovascularization in ischemic tissue, but the mechanism of EPCs homing to the site of ischemia is poorly understood. In this study, to investigate the mechanism of human umbilical cord blood-derived high proliferative potential-endothelial progenitor cells (HPP-EPCs) homing to ischemic tissue we evaluated the expression of lymphocyte function-associated antigen-1 (LFA-1, or CD11a/CD18) and very late antigen-4 (VLA-4, or CD49d/CD29) in EPCs and the changes of expression level of their ligands, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), in ischemic tissue and performed the adhesion and migration assays to analyze the interaction between the receptors and ligands. Furthermore, we studied the roles of LFA-1 and VLA-4 in EPC homing in an ischemic model of mice. The results show that LFA-1 andVLA-4 were expressed in HPPEPCs and ICAM-1 and VCAM-1 were expressed in vessel endothelium in ischemic tissues. The pre-incubation of HPP-EPCs with neutralizing antibodies against CD11a or CD49d reduced adhesion and migration of HPP-EPCs in vitro and reduced recovery of hind-limb blood flow, capillary density and incorporation of HPP-EPC into ischemic tissues in vivo. Furthermore, the pre-incubation of HPP-EPCs with the combination of CD11a and CD49d antibodies led to synergistically negative effects on adhesion and transmigration of HPP-EPCs in vitro, and on the homing of HPP-EPCs to ischemic tissue and on neovascularization capacity in vivo. These results indicate that LFA-1 andVLA-4 are involved in HPP-EPC homing to ischemic tissues.

Animals↗
PubMed2005

alphavbeta3- and alpha5beta1-integrin blockade inhibits myogenic constriction of skeletal muscle resistance arterioles.

In isolated resistance arterioles with spontaneous tone, ligation of alpha4beta1- and alpha5beta1-integrins induces vasoconstriction whereas ligation of alphavbeta3-integrin induces vasodilation. However, whether integrins directly participate in myogenic constriction to pressure elevation is not known. To answer this question, isolated rat skeletal muscle arterioles were exposed to step increments in pressure in the absence or presence of peptides and function-blocking antibodies known to bind alpha4beta1-, alpha5beta1-, or alphavbeta3-integrins while vessel diameter was continually monitored. Myogenic constriction, as assessed by the ability of isolated arterioles to reduce their diameter in response to two consecutive increments in intraluminal pressure (90-110 and 110-130 cmH2O), was not affected by treatment with any of the control peptides (RAD, LEV), a control antibody (anti-rat major histocompatibility complex), an alpha4beta1-integrin-binding peptide (LDV), or an anti-alpha4-integrin antibody. In contrast, alpha5beta1-integrin blockade with either anti-alpha5- or anti-beta1-integrin antibody caused a significant inhibition of myogenic constriction. Also, both RGD peptide and anti-beta3-integrin antibody inhibited myogenic constriction. These results indicate that alpha5beta1- and alphavbeta3-integrins are necessary for myogenic constriction and further suggest that integrins are part of the mechanosensory apparatus responsible for the ability of vascular smooth muscle cells to detect and/or respond to changes in intraluminal pressure.

Animals↗
PubMed2002

Integrin-mediated long-term B cell retention in the splenic marginal zone.

The mechanisms that control localization of marginal zone (MZ) B cells are poorly understood. Here we show that MZ B cells express elevated levels of the integrins LFA-1 (alphaLbeta2) and alpha4beta1 and that they bind to the ligands ICAM-1 and VCAM-1. These ligands are expressed within the MZ in a lymphotoxin-dependent manner. Combined inhibition of LFA-1 and alpha4beta1 causes a rapid and selective release of B cells from the MZ. Furthermore, lipopolysaccharide-triggered MZ B cell relocalization involves down-regulation of integrin-mediated adhesion. These studies identify key requirements for MZ B cell localization and establish a role for integrins in peripheral lymphoid tissue compartmentalization.

Animals↗
PubMed1999

Selective eosinophil transendothelial migration triggered by eotaxin via modulation of Mac-1/ICAM-1 and VLA-4/VCAM-1 interactions.

We have recently cloned eotaxin, a highly efficacious eosinophilic chemokine involved in the development of lung eosinophilia during allergic inflammatory reactions. To understand more precisely how eotaxin facilitates the specific migration of eosinophils, we have studied which adhesion receptors are essential for eotaxin action both in vivo and in vitro. Experiments using mice genetically deficient in adhesion receptors demonstrated that molecules previously reported to be involved in both leukocyte tethering/rolling (P-selectin and E-selectin) and in sticking/ transmigration (ICAM-1 and VCAM-1) are required for eotaxin action in vivo. To further elucidate the mechanism(s) involved in this process, we have used an in vitro transendothelial chemotaxis model. mAb neutralization studies performed in this system suggest that the integrins Mac-1 (CD11b/18), VLA-4 (alpha4beta1) and LFA-1 (CD11a/18) are involved in the transendothelial chemotaxis of eosinophils to eotaxin. Accordingly, the expression of these integrins on eosinophils is elevated by direct action of this chemokine in a concentration-dependent manner. Taken together, our results suggest that eotaxin-induced eosinophil transendothelial migration in vivo and in vitro relies on Mac-1/ICAM-1 and VLA-4NCAM-1 interactions, the latter ones becoming more relevant at later time points of the eotaxin-induced recruitment process.

Animals↗
PubMed2000

Expression and functional activity of the very late activation antigen-4 molecule on human natural killer cells in different states of activation.

In the present study we describe the expression and functional activity of the alpha4beta1 heterodimer molecule on human natural killer (NK) cells. Flow cytometric analyses showed that fresh and activated NK cells expressed high levels of very late activation antigen-4 (VLA-4) molecules. These cells bound to fibronectin (FN) and to its 38 000-MW proteolytic fragment through the VLA-4 integrin that was blocked with HP2/1 anti-alpha4 monoclonal antibodies (mAbs) and with the FN peptide fragment CS1. No inhibitory effects were observed in the presence of anti-alpha5 mAb, FN peptide fragment CS2 or other irrelevant mAb. Fresh NK cells were unable to aggregate, despite their expression of VLA-4, and only activated (cultured and lymphocyte-activated killer cells) NK cells showed homotypic aggregation with HP1/7 and HP2/4 anti-alpha4 mAb related to cellular activation. These results underline new evidence of how NK cells in different states of activation maintain different constitutive levels of alpha4beta1 integrin activity, and highlight the possibility of a different functional regulation by the cells bearing VLA-4, in the expression of these epitopes and their ability to interact with their ligands.

Cell Adhesion↗
PubMed2003

Effect of food on pharmacokinetics of an inhaled drug: a case study with a VLA-4 antagonist, HMR1031.

HMR1031 is a potent and specific antagonist of the integrin VLA-4 (alpha4beta1) binding to vascular cell adhesion molecule-1 (VCAM-1) and fibronectin. HMR1031 is an inhaled drug being developed for the treatment of asthma using an Ultrahaler dry-powder inhalation device. A pharmacoscintigraphic study of HMR1031 suggests a lung deposition of approximately 25% and gastrointestinal tract deposition of approximately 75%. Since oral absorption may be contributing to systemic plasma concentrations, the effect of food on HMR1031 was assessed. This was a single-dose (3 mg), open-label, randomized, two-way crossover (fasted vs. fed) study in 8 healthy male subjects. Blood samples were collected at predose and up to 24 hours postdose. Plasma concentrations were determined by the LC/MS/MS method. HMR1031 was rapidly absorbed, with median tmax values of 1.0 and 0.75 hours under fasted and fed conditions, respectively. Under fasted conditions, mean AUCinfinity and Cmax values were 16.4 ng x h/mL and 4.56 ng/mL, respectively. Under fed conditions, mean AUCinfinity and Cmax values decreased to 11.7 ng x h/mL and 2.81 ng/mL, respectively. The mean terminal elimination half-life (t1/2) for both treatment groups was similar (2.7 h). HMR1031 population estimates of the apparent clearance, apparent volume of distribution, and absorption rate were 225 L/h (4.1% coefficient of variation [CV]), 44.5 L (26% CV), and 0.340 h-1 (7.0% CV), respectively. Food is a significant covariate on clearance. These data suggest that food unexpectedly decreases the systemic exposure of inhaled HMR1031 by approximately 30%, probably due to increased liver blood flow and increased biliary excretion. This decrease in systemic exposure is unlikely to affect the topical effect of the drug but may result in increased variability in plasma pharmacokinetics. The disposition and food effect of HMR1031 can be described using mixed-effect modeling.

Absorption↗
PubMed2000

Infusion of an antialpha4 integrin antibody is associated with less neoadventitial formation after balloon injury of porcine coronary arteries.

BACKGROUND: The alpha4beta1 (or very late antigen-4 [VLA-4]) integrin is thought to play a role in inflammatory processes, mediating mononuclear leukocyte infiltration. The adventitial response to balloon injury is an important determinant of neointimal formation and arterial remodelling. OBJECTIVES: To determine whether the monoclonal antibody hHP1/2 directed against the human alpha4-integrin subunit decreases neoadventitial formation and subsequent luminal narrowing following balloon injury. DESIGN: Randomized, double-blind, placebo controlled study. SETTING: Tertiary care, Canadian university hospital vascular biology laboratory. ANIMALS AND METHODS: In 16 pigs, two coronary arteries were injured with an oversized balloon, while a third coronary artery was designated as an uninjured control vessel. One hour before balloon injury, 5 mg/kg of hHP1/2 was administered to eight animals, while another eight animals received an infusion of a saline placebo. Animals were killed three and 14 days following balloon injury. MAIN RESULTS: Administration of hHP1/2 resulted in an immediate decrease in circulating monocyte and lymphocyte counts. These parameters returned to normal within three days. There was a decrease in neoadventitial formation 14 days after arterial injury in pigs treated with hHP1/2 compared with controls (2.26+/-0.77 versus 3.42+/-1.01 mm, respectively, P=0.04). There was a loss of lumen area between days 3 (4.33+/-1.09 mm2) and 14 (3.09+/-0.38 mm2, P=0.02) after balloon injury in pigs treated with saline, but not in the pigs treated with hHP1/2. CONCLUSIONS: Administration of an antibody to the alpha4-integrin subunit is associated with less neoadventitial formation and less lumenal narrowing after balloon injury. This novel therapy may play an important role in modulating arterial remodelling and thereby may reduce restenosis following percutaneous coronary interventions in humans.

Angioplasty, Balloon, Coronary↗
PubMed1999

Expression and function of cell adhesion molecules on fetal liver, cord blood and bone marrow hematopoietic progenitors: implications for anatomical localization and developmental stage specific regulation of hematopoiesis.

The mechanism of localization, migration, and regulation of hematopoiesis at different stages of ontogeny is not well understood, but may relate to the specific adhesive interactions between hematopoietic stem cells and their microenvironment at different ontogenic stages. We studied the expression of cell adhesion molecules (CAM) on fetal liver (FL), umbilical cord blood (UCB) and adult bone marrow (ABM) CD34+ cells, and the adhesion of committed progenitors (CFC) from all three sources to ABM stromal layers and purified extracellular matrix proteins. Compared to ABM CFC, significantly more UCB CFC and fewer FL CFC adhered to ABM stroma. Adhesion of FL CFC to fibronectin (FN), the 75 kD RGD containing FN fragment and the 33-66 kD COOH-terminal heparin binding FN fragment was also significantly less than that of ABM CFC. Like ABM CFC, the adhesion of FL CFC was mediated through alpha4beta1 and alpha5beta1 integrins. Of note, more FL CD34+ cells expressed alpha5 integrins and the number of alpha4, alpha5 and beta1 integins per cell (mean channel frequency) was similar or higher for FL CD34+ cells than ABM CD34+ cells. Further, treatment of FL CFC with a beta1 integrin activating antibody (8A2), increased adhesion of FL CFC to FN to the same level as that of 8A2 treated ABM CFC. This suggests that the alpha4beta1 and alpha5beta1 integrins on FL CD34+ cells may be present in a low avidity/affinity state. We also show that unlike ABM, FL CD34+ cells expressed alpha2 and that approximately 20% FL CFC adhered to collagen IV. Further, alpha2beta1 integrin on FL CFC was functional since their engagement, either by adhesion to collagen IV or through blocking alpha2 antibodies, transmitted proliferation inhibitory signals. In contrast to alpha4b and alpha5beta1 integrin dependent adhesion, alpha2beta1 dependent adhesion of FL CFC to collagen IV was not enhanced after treatment with 8A2. The reason for this is not clear but suggests that alpha2 integrins on FL CFC are maximally activated. This novel adhesive interaction with collagen IV, reminiscent of that described for CML progenitors, may have a role in the extramedullary localization of FL hematopoiesis or its developmental stage-specific regulation by its microenvironment. Studies to evaluate these possibilities are underway.

Adult↗